Isoxazoline derivatives as insecticides

ABSTRACT

The present invention relates to compounds formula (I): 
                         
wherein
 
P is P1, P2, heterocyclyl or heterocyclyl substituted by one to five Z;
 
                         
and wherein A 1 , A 2 , A 3 , A 4 , G 1 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 17 , R 18 , R 19  and R 20  are as defined herein; or a salt or N-oxide thereof.
 
     Furthermore, the present invention relates to processes and intermediates for preparing compounds of formula (I), to insecticidal, acaricidal, nematicidal and molluscicidal compositions comprising the compounds of formula (I) and to methods of using the compounds of formula (I) to control insect, acarine, nematode and mollusc pests.

RELATED APPLICATION INFORMATION

This application is a divisional of U.S. patent application Ser. No.13/579,637 which was filed on Aug. 17, 2012 which is a 371 ofInternational Application No. PCT/EP2011/052336, filed Feb. 17, 2011,which claims priority to EP Patent Application No. 10153831.2, filedFeb. 17, 2010, the contents of which are incorporated herein byreference herein.

The present invention relates to certain 2,5-dihydro-isoxazolinederivatives, to processes and intermediates for preparing thesederivatives, to insecticidal, acaricidal, nematicidal and molluscicidalcompositions comprising these derivatives and to methods of using thesederivatives to control insect, acarine, nematode and mollusc pests.

Certain 4,5-dihydro-isoxazoline derivatives with insecticidal propertiesare disclosed, for example, in EP 1,731,512.

It has now surprisingly been found that certain 2,5-dihydro-isoxazolinederivatives have insecticidal properties.

The present invention therefore provides a compound of formula (I)

whereinP is P1, P2, heterocyclyl or heterocyclyl substituted by one to five Z;

A¹, A², A³ and A⁴ are independently of each other C—H, C—R⁷, ornitrogen;G¹ is oxygen or sulfur,R¹ is hydrogen, C₁-C₈alkyl, C₁-C₈alkoxy-, C₁-C₈alkylcarbonyl-, orC₁-C₈alkoxycarbonyl-;R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁸,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R⁹,aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moiety issubstituted by one to five R¹⁰, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R¹⁰, aryl or aryl substituted by one to fiveR¹⁰, heterocyclyl or heterocyclyl substituted by one to five R¹⁰,C₁-C₈alkylaminocarbonyl-C₁-C₄alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄alkylene,C₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄alkylene, C₁-C₆alkyl-O—N═CH—, orC₁-C₆haloalkyl-O—N═CH—;R³ is C₁-C₈haloalkyl;R⁴ is aryl or aryl substituted by one to five R¹¹, or heteroaryl orheteroaryl substituted by one to five R¹¹;R⁵ is hydrogen;R⁶ is hydrogen, C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R¹²,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R¹³,aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moiety issubstituted by one to five R¹⁴, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R¹⁴, aryl or aryl substituted by one to fiveR¹⁴, heterocyclyl or heterocyclyl substituted by one to five R¹⁴,C₁-C₄alkoxycarbonyl-, C₁-C₄alkenyloxycarbonyl-,C₁-C₄alkynyloxycarbonyl-, or benzyloxycarbonyl- or benzyloxycarbonyl- inwhich the benzyl group is optionally substituted by one to five R¹⁶;each R⁷ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkenyl, C₁-C₈haloalkenyl, C₁-C₈alkynyl,C₁-C₈haloalkynyl, C₃-C₁₀cycloalkyl, C₁-C₈alkoxy-, C₁-C₈haloalkoxy-,C₁-C₈alkylthio-, C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-,C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, orC₁-C₈haloalkylsulfonyl-;each R⁸ is independently halogen, cyano, nitro, hydroxy, amino,C₁-C₈alkylamino, (C₁-C₈alkyl)₂-amino, C₁-C₈alkylcarbonylamino,C₁-C₈haloalkylcarbonylamino, C₁-C₈alkoxy-, C₁-C₈haloalkoxy-, aryloxy oraryloxy substituted by one to five R¹⁵, aryloxy-C₁-C₄alkylene oraryloxy-C₁-C₄alkylene wherein the aryl moiety is substituted by one tofive R⁵, C₁-C₈alkylcarbonyl-, C₁-C₈alkoxycarbonyl-, mercapto,C₁-C₈alkylthio-, C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-,C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, C₁-C₈haloalkylsulfonyl-,or aryl-C₁-C₄alkylthio- or aryl-C₁-C₄alkylthio- wherein the aryl moietyis substituted by one to five R¹⁵;each R⁹ is independently halogen, C₁-C₈alkyl, C₁-C₈alkenyl,C₁-C₈alkynyl, C₁-C₈alkyl-O—N═, C₁-C₈haloalkyl-O—N═, C₁-C₈alkoxy orC₁-C₈alkoxycarbonyl;each R¹⁰ is independently halogen, cyano, nitro, oxo, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈cyanoalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl,C₂-C₈alkynyl, C₂-C₈haloalkynyl, C₃-C₁₀cycloalkyl,C₃-C₁₀cycloalkyl-C₁-C₄alkylene, hydroxy, C₁-C₈alkoxy-, C₁-C₈haloalkoxy-,mercapto, C₁-C₈alkylthio-, C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-,C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, C₁-C₈haloalkylsulfonyl-,C₁-C₈alkylaminosulfonyl, (C₁-C₈alkyl)₂-aminosulfonyl-,C₁-C₈alkylcarbonyl-, C₁-C₈alkoxycarbonyl-, aryl or aryl substituted byone to five R¹⁵, heterocyclyl or heterocyclyl substituted by one to fiveR¹⁵, aryl-C₁-C₄alkylene or aryl-C₁-C₄alkylene wherein the aryl moiety issubstituted by one to five R¹⁵, heterocyclyl-C₁-C₄alkylene orheterocyclyl-C₁-C₄alkylene wherein the heterocyclyl moiety issubstituted by one to five R¹⁵, aryloxy or aryloxy substituted by one tofive R¹⁵, aryloxy-C₁-C₄alkylene or aryloxy-C₁-C₄alkylene wherein thearyl moiety is substituted by one to five R¹⁵;each R¹¹ and R¹⁴ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl, C₂-C₈alkynyl,C₂-C₈haloalkynyl, hydroxy, C₁-C₈alkoxy-, C₁-C₈haloalkoxy-, mercapto,C₁-C₈alkylthio-, C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-,C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, C₁-C₈haloalkylsulfonyl-,C₁-C₈alkylcarbonyl-, C₁-C₈alkoxycarbonyl-, aryl or aryl substituted byone to five R¹⁵, or heterocyclyl or heterocyclyl substituted by one tofive R¹⁵;each R¹² is independently halogen, cyano, nitro, hydroxy, C₁-C₈alkoxy-,C₁-C₈haloalkoxy-, C₁-C₈alkylcarbonyl-, C₁-C₈alkoxycarbonyl-, mercapto,C₁-C₈alkylthio-, C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-,C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, orC₁-C₈haloalkylsulfonyl-;each R¹³ is independently halogen or C₁-C₈alkyl;each R¹⁵ is independently halogen, cyano, nitro, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy-, or C₁-C₄haloalkoxy-;each R¹⁶ is independently halogen, cyano, formyl, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₃-C₆cycloalkyl;R¹⁷ and R¹⁸ are independently halogen, hydrogen, C₁-C₁₂alkyl orC₁-C₁₂alkyl substituted by one to five R⁸, C₃-C₈cycloalkyl orC₃-C₈cycloalkyl substituted by one to five R⁹, C₂-C₁₂alkenyl orC₂-C₁₂alkenyl substituted by one to five R⁸, C₂-C₁₂alkynyl orC₂-C₁₂alkynyl substituted by one to five R⁸, cyano, C₁-C₁₂alkoxycarbonylor C₁-C₁₂alkoxycarbonyl substituted by one to five R⁸,C₁-C₁₂alkoxythiocarbonyl or C₁-C₁₂alkoxythiocarbonyl substituted by oneto five R⁸, or R¹⁷ and R¹⁸ together with the carbon atom to which theyare attached may form a 3 to 6-membered carbocyclic ring;R¹⁹ is hydrogen, NH₂, hydroxyl, C₁-C₁₂alkoxy or C₁-C₁₂alkoxy substitutedby one to five R⁸, C₁-C₁₂alkylcarbonylamino or C₁-C₁₂alkylcarbonylaminowherein the alkyl is substituted by one to five R⁸, C₁-C₁₂alkylamino orC₁-C₁₂alkylamino wherein the alkyl is substituted by one to five R⁸,C₁-C₁₂alkyl or C₁-C₁₂alkyl substituted by one to five R⁸,C₃-C₈cycloalkyl or C₃-C₈cycloalkyl substituted by one to five R⁹, cyano,C₂-C₁₂alkenyl or C₂-C₁₂alkenyl substituted by one to five R⁸,C₂-C₁₂alkynyl or C₂-C₁₂alkynyl substituted by one to five R⁸,C₁-C₁₂alkylcarbonyl or C₁-C₁₂alkylcarbonyl substituted by one to fiveR⁸, C₁-C₁₂alkoxycarbonyl or C₁-C₁₂alkoxycarbonyl substituted by one tofive R⁸, or is selected from CH₂—R²¹, C(═O)R²¹ and C(═S)R²¹;R²⁰ is hydrogen, cyano, carbonyl, thiocarbonyl, C₁-C₁₂alkylcarbonyl orC₁-C₁₂alkylcarbonyl substituted by one to five R⁸,C₁-C₁₂alkylthiocarbonyl or C₁-C₁₂alkylthiocarbonyl substituted by one tofive R⁸, C₁-C₁₂alkylaminocarbonyl or C₁-C₁₂alkylaminocarbonyl whereinthe alkyl is substituted by one to five R⁸, C₁-C₁₂alkylaminothiocarbonylor C₁-C₁₂alkylaminothiocarbonyl wherein the alkyl is substituted by oneto five R⁸, C₂-C₂₄ (total carbon number) dialkylaminocarbonyl or C₂-C₂₄(total carbon number) dialkylaminocarbonyl wherein one or both alkyl issubstituted by one to five R⁸, C₂-C₂₄ (total carbon number)dialkylaminothiocarbonyl or C₂-C₂₄ (total carbon number)dialkylaminothiocarbonyl wherein one or both alkyl is substituted by oneto five R⁸, C₁-C₁₂alkoxyaminocarbonyl or C₁-C₁₂alkoxyaminocarbonylwherein the alkoxy is substituted by one to five R⁸,C₁-C₁₂alkoxyaminothiocarbonyl or C₁-C₁₂alkoxyaminothiocarbonyl whereinthe alkoxy is substituted by one to five R⁸, C₁-C₁₂alkoxycarbonyl orC₁-C₁₂alkoxycarbonyl substituted by one to five R⁸,C₁-C₁₂alkoxythiocarbonyl or C₁-C₁₂alkoxythiocarbonyl substituted by oneto five R⁸, C₁-C₁₂thioalkoxycarbonyl or C₁-C₁₂thioalkoxycarbonylsubstituted by one to five R⁸, C₁-C₁₂thioalkoxythiocarbonyl orC₁-C₁₂thioalkoxythiocarbonyl substituted by one to five R⁸,C₁-C₁₂alkylsulfonyl or C₁-C₁₂alkylsulfonyl substituted by one to fiveR⁸, C₃-C₁₂cycloalkylcarbonyl or C₃-C₁₂cycloalkylcarbonyl substituted byone to five R⁹, C₂-C₁₂alkenylcarbonyl or C₂-C₁₂alkenylcarbonylsubstituted by one to five R⁸, C₂-C₁₂alkynylcarbonyl orC₂-C₁₂alkynylcarbonyl substituted by one to five R⁸,C₃-C₁₂cycloalkyl-C₁-C₁₂alkylcarbonyl orC₃-C₁₂cycloalkyl-C₁-C₁₂alkylcarbonyl substituted by one to five R⁹,C₁-C₂alkylsulfenyl-C₁-C₂alkylcarbonyl orC₁-C₂alkylsulfenyl-C₁-C₂alkylcarbonyl substituted by one to five R⁸,C₁-C₁₂ alkylsulfinyl-C₁-C₁₂alkylcarbonyl or C₁-C₁₂alkylsulfinyl-C₁-C₁₂alkylcarbonyl substituted by one to five R⁸, C₁-C₁₂alkylsulfonyl-C₁-C₁₂alkylcarbonyl orC₁-C₁₂alkylsulfonyl-C₁-C₁₂alkylcarbonyl substituted by one to five R⁸,C₁-C₁₂alkylcarbonyl-C₁-C₁₂alkylcarbonyl orC₁-C₁₂alkylcarbonyl-C₁-C₁₂alkylcarbonyl substituted by one to five R⁸,C₃-C₁₂ cycloalkylaminocarbonyl or C₃-C₁₂cycloalkylaminocarbonyl whereinthe cycloalkyl is substituted by one to five R⁹,C₂-C₁₂alkenylaminocarbonyl or C₂-C₁₂alkenylaminocarbonyl wherein thealkenyl is substituted by one to five R⁸, C₂-C₁₂alkynylaminocarbonyl orC₂-C₁₂alkynylaminocarbonyl wherein the alkynyl is substituted by one tofive R⁸, or is selected from C(═O)R²¹ and C(═S)R²¹;or R¹⁹ and R²⁰ together with the nitrogen atom to which they are bound,form a 3- to 6-membered heterocyclic ring which may be substituted byone to five R², or may be substituted with a keto, thioketo ornitroimino group;R²¹ is aryl or aryl substituted by one to five R², heterocyclyl orheterocyclyl substituted by one to five R², aryl-C₁-C₄alkylene oraryl-C₁-C₄alkylene wherein the aryl moiety is substituted by one to fiveR², or heterocyclyl-C₁-C₄alkylene or heterocyclyl-C₁-C₄alkylene whereinthe heterocyclyl moiety is substituted by one to five R²²;each R² is independently halogen, cyano, nitro, oxo, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₁-C₈alkoxycarbonyl,C₁-C₈alkyl-N═, C₁-C₈haloalkyl-N═, C₁-C₈alkylthio, C₁-C₈haloalkylthio, orphenyl or phenyl substituted by one to five halogen;each Z is independently halogen, C₁-C₁₂alkyl or C₁-C₁₂alkyl substitutedby one to five R⁸, nitro, C₁-C₁₂alkoxy or C₁-C₁₂alkoxy substituted byone to five R⁸, cyano, C₁-C₁₂alkylsulfinyl, C₁-C₁₂alkylsulfonyl,C₁-C₁₂haloalkylsulfinyl, C₁-C₁₂haloalkylsulfonyl, hydroxyl or thiol; ora salt or N-oxide thereof.

The compounds of formula (I) may exist in different geometric or opticalisomers or tautomeric forms. This invention covers all such isomers andtautomers and mixtures thereof in all proportions as well as isotopicforms such as deuterated compounds.

The compounds of the invention may contain one or more asymmetric carbonatoms, for example, at the —CR³R⁴— group, and may exist as enantiomers(or as pairs of diastereo-isomers) or as mixtures of such.

Alkyl groups (either alone or as part of a larger group, such asalkoxy-, alkylthio-, alkylsulfinyl-, alkylsulfonyl-, alkylcarbonyl- oralkoxycarbonyl-) can be in the form of a straight or branched chain andare, for example, methyl, ethyl, propyl, prop-2-yl, butyl, but-2-yl,2-methyl-prop-1-yl or 2-methyl-prop-2-yl. The alkyl groups arepreferably C₁-C₆, more preferably C₁-C₄, most preferably C₁-C₃ alkylgroups. Where an alkyl moiety is said to be substituted, the alkylmoiety is preferably substituted by one to four substituents, mostpreferably by one to three substituents.

Alkylene groups can be in the form of a straight or branched chain andare, for example, —CH₂—, —CH₂—CH₂—, —CH(CH₃)—, —CH₂—CH₂—CH₂—,—CH(CH₃)—CH₂—, or —CH(CH₂CH₃)—. The alkylene groups are preferablyC₁-C₃, more preferably C₁-C₂, most preferably C₁ alkylene groups.

Alkenyl groups can be in the form of straight or branched chains, andcan be, where appropriate, of either the (E)- or (Z)-configuration.Examples are vinyl and allyl. The alkenyl groups are preferably C₂-C₆,more preferably C₂-C₄, most preferably C₂-C₃ alkenyl groups.

Alkynyl groups can be in the form of straight or branched chains.Examples are ethynyl and propargyl. The alkynyl groups are preferablyC₂-C₆, more preferably C₂-C₄, most preferably C₂-C₃ alkynyl groups.

Halogen is fluorine, chlorine, bromine or iodine.

Haloalkyl groups (either alone or as part of a larger group, such ashaloalkoxy-, haloalkylthio-, haloalkylsulfinyl- or haloalkylsulfonyl-)are alkyl groups which are substituted by one or more of the same ordifferent halogen atoms and are, for example, difluoromethyl,trifluoromethyl, chlorodifluoromethyl or 2,2,2-trifluoro-ethyl.

Haloalkenyl groups are alkenyl groups which are substituted by one ormore of the same or different halogen atoms and are, for example,2,2-difluoro-vinyl or 1,2-dichloro-2-fluoro-vinyl.

Haloalkynyl groups are alkynyl groups which are substituted by one ormore of the same or different halogen atoms and are, for example,1-chloro-prop-2-ynyl.

Cycloalkyl groups or carbocyclic rings can be in mono- or bi-cyclic formand are, for example, cyclopropyl, cyclobutyl, cyclohexyl andbicyclo[2.2.1]heptan-2-yl. The cycloalkyl groups are preferably C₃-C₈,more preferably C₃-C₆ cycloalkyl groups. Where a cycloalkyl moiety issaid to be substituted, the cycloalkyl moiety is preferably substitutedby one to four substituents, most preferably by one to threesubstituents.

Aryl groups (either alone or as part of a larger group, such asaryl-alkylene-) are aromatic ring systems which can be in mono-, bi- ortricyclic form. Examples of such rings include phenyl, naphthyl,anthracenyl, indenyl or phenanthrenyl. Preferred aryl groups are phenyland naphthyl, phenyl being most preferred. Where an aryl moiety is saidto be substituted, the aryl moiety is preferably substituted by one tofour substituents, most preferably by one to three substituents.

Heteroaryl groups (either alone or as part of a larger group, such asheteroaryl-alkylene-) are aromatic ring system containing at least oneheteroatom and consisting either of a single ring or of two or morefused rings. Preferably, single rings will contain up to threeheteroatoms and bicyclic systems up to four heteroatoms which willpreferably be chosen from nitrogen, oxygen and sulfur. Examples ofmonocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,pyrrolyl, pyrazolyl, imidazolyl, triazolyl, furanyl, thiophenyl,oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl andthiadiazolyl. Examples of bicyclic groups include quinolinyl,cinnolinyl, quinoxalinyl, indolyl, indazolyl, benzimidazolyl,benzothiophenyl and benzothiazolyl. Monocyclic heteroaryl groups arepreferred, pyridyl being most preferred. Where a heteroaryl moiety issaid to be substituted, the heteroaryl moiety is preferably substitutedby one to four substituents, most preferably by one to threesubstituents.

Heterocyclyl groups or heterocyclic rings (either alone or as part of alarger group, such as heterocyclyl-alkylene-) are defined to includeheteroaryl groups and in addition their unsaturated or partiallyunsaturated analogues. Examples of monocyclic groups include thietanyl,pyrrolidinyl, tetrahydrofuranyl, [1,3]dioxolanyl, piperidinyl,piperazinyl, [1,4]dioxanyl, and morpholinyl or their oxidised versionssuch as 1-oxo-thietanyl and 1,1-dioxo-thietanyl. Examples of bicyclicgroups include 2,3-dihydro-benzofuranyl, benzo[1,3]dioxolanyl, and2,3-dihydro-benzo[1,4]dioxinyl. Where a heterocyclyl moiety is said tobe substituted, the heterocyclyl moiety is preferably substituted by oneto four substituents, most preferably by one to three substituents.

Preferred values of P, A¹, A², A³, A⁴, G¹, R¹, R², R³, R⁴, R⁶, R⁷, R⁸,R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R²⁰, R²¹ and R²²are, in any combination, as set out below.

Preferably, P is P1, P2, or a heterocycle selected from H1 to H9

k is 0, 1 or 2.

In one group of compounds P is P1. In another group of compounds P isP2. In another group of compounds P is a heterocycle selected fromH1-H9.

Preferably no more than two of A¹, A², A³ and A⁴ are nitrogen, morepreferably no more than one of A¹, A², A³ and A⁴ is nitrogen.

Preferably no more than two of A¹, A², A³ and A⁴ are nitrogen.

Preferably A¹ is C—H or C—R⁷, most preferably A¹ is C—R⁷.

Preferably A² is C—H or C—R⁷, most preferably A² is C—H.

Preferably A³ is C—H or C—R⁷, most preferably A³ is C—H.

Preferably A⁴ is C—H or C—R⁷, most preferably A⁴ is C—H.

In one preferred group of compounds A¹ is C—R⁷, A² is C—H, A³ is C—H ornitrogen and A⁴ is C—H or nitrogen.

In another preferred group of compounds A¹ is C—R⁷, A² is C—H, A³ is C—Hand A⁴ is C—H.

Preferably G¹ is oxygen.

Preferably R¹ is hydrogen, methyl, ethyl, methylcarbonyl-, ormethoxycarbonyl-, more preferably hydrogen, methyl or ethyl, mostpreferably hydrogen.

Preferably, R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to fiveR⁸, C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R⁹,aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moiety issubstituted by one to five R¹⁰, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R¹⁰, aryl or aryl substituted by one to fiveR¹⁰, heterocyclyl or heterocyclyl substituted by one to five R¹⁰,C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene,C₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene, or group A

wherein R²³ is hydrogen, methyl, ethyl, propyl, isopropyl, butyl,cyclopropyl, cyclopropyl-methyl, cyclobutyl, cyclobutyl-methyl,oxetanyl, thietanyl, trifluoroethyl, difluoroethyl, allyl, propargyl,cyanomethyl, benzyl, benzyl substituted by one to three R¹², or R¹¹ ispyridyl-methyl- or pyridyl-methyl-substituted by one to three R¹²; andeach R¹² is independently fluoro, chloro, bromo, trifluoromethyl,trifluoromethoxy, cyano or methoxy. Preferably each aryl group is aphenyl group and each heterocycle group is selected from pyridyl,pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl, imidazolyl,triazolyl, tetrahydrothiophenyl, tetrazolyl, furanyl, thiophenyl,oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl,thiadiazolyl, quinolinyl, cinnolinyl, quinoxalinyl, indolyl, indazolyl,benzimidazolyl, benzothiophenyl, benzothiazolyl, oxetanyl, thietanyl,oxo-thietanyl, dioxo-thietanyl, pyrrolidinyl, tetrahydrofuranyl,[1,3]dioxolanyl, piperidinyl, piperazinyl, [1,4]dioxanyl, andmorpholinyl, 2,3-dihydro-benzofuranyl, benzo[1,3]dioxolanyl, and2,3-dihydro-benzo[1,4]-dioxinyl.

Preferably R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁸,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R⁹,aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moiety issubstituted by one to five R¹⁰, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R¹⁰, aryl or aryl substituted by one to fiveR¹⁰, heterocyclyl or heterocyclyl substituted by one to five R¹⁰,C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene, wherein each aryl group isa phenyl group and each heterocycle group is selected from pyridyl,pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl, imidazolyl,triazolyl, tetrahydrothiophenyl, tetrazolyl, furanyl, thiophenyl,oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl,thiadiazolyl, quinolinyl, cinnolinyl, quinoxalinyl, indolyl, indazolyl,benzimidazolyl, benzothiophenyl, benzothiazolyl, oxetanyl, thietanyl,oxo-thietanyl, dioxo-thietanyl, pyrrolidinyl, tetrahydrofuranyl,[1,3]dioxolanyl, piperidinyl, piperazinyl, [1,4]dioxanyl, andmorpholinyl, 2,3-dihydro-benzofuranyl, benzo[1,3]dioxolanyl, and2,3-dihydro-benzo[1,4]dioxinyl.

More preferably R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one tofive R⁸, C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to fiveR⁹, aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moietyis substituted by one to five R¹⁰, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R¹⁰, aryl or aryl substituted by one to fiveR¹⁰, heterocyclyl or heterocyclyl substituted by one to five R¹⁰,C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene, wherein each aryl group isa phenyl group and each heterocycle group is selected from 1,2,3triazolyl, 1,2,4 triazolyl, tetrazolyl, pyrimidinyl, pyrazinyl,pyridazinyl, tetrahydrothiophenyl, isoxazolinyl, pyridyl,tetrahydrofuranyl, imidazolyl, pyrazolyl, pyrrolyl, thiazolyl, oxetanyl,thietanyl, oxo-thietanyl and dioxo-thietanyl.

More preferably still R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by oneto five R⁸, C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one tofive R⁹, aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the arylmoiety is substituted by one to five R¹⁰, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R¹⁰, aryl or aryl substituted by one to fiveR¹⁰, heterocyclyl or heterocyclyl substituted by one to five R¹⁰,C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene, wherein each aryl group isa phenyl group and each heterocycle group is selected from pyridyl,tetrahydrofuranyl, imidazolyl, pyrazolyl, pyrrolyl, thiazolyl, oxetanyl,thietanyl, oxo-thietanyl and dioxo-thietanyl.

More preferably still R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by oneto five R⁸, C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one tofive R⁹, phenyl-C₁-C₄alkylene- or phenyl-C₁-C₄alkylene- wherein thephenyl moiety is substituted by one to five R¹⁰, pyridyl-C₁-C₄alkylene-or pyridyl-C₁-C₄alkylene- wherein the pyridyl moiety is substituted byone to four R¹⁰, tetrahydrofuranyl-C₁-C₄alkylene- ortetrahydrofuranyl-C₁-C₄alkylene- wherein the tetrahydrofuranyl moiety issubstituted by one to five R¹⁰, imidazolyl-C₁-C₄alkylene- orimidazolyl-C₁-C₄alkylene- wherein the imidazolyl moiety is substitutedby one to three R¹⁰, pyrazolyl-C₁-C₄alkylene- orpyryazolyl-C₁-C₄alkylene- wherein the pyrazolyl moiety is substituted byone to three R¹⁰, pyrrolyl-C₁-C₄alkylene- or pyrrolyl-C₁-C₄alkylene-wherein the pyrrolyl moiety is substituted by one to four R¹⁰,thiazolyl-C₁-C₄alkylene- or thiazolyl-C₁-C₄alkylene- wherein thethiazolyl moiety is substituted by one to four R¹⁰, oxetanyl or oxetanylsubstituted by one to five R¹⁰, thietanyl or thietanyl substituted byone to five R¹⁰, oxo-thietanyl or oxo-thietanyl substituted by one tofive R¹⁰, dioxo-thietanyl or dioxo-thietanyl substituted by one to fiveR¹⁰, C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene, for example C₁-C₈alkyl orC₁-C₈alkyl substituted by one to five R⁸, C₃-C₁₀cycloalkyl orC₃-C₁₀cycloalkyl substituted by one to five R⁹, phenyl-C₁-C₄alkylene- orphenyl-C₁-C₄alkylene- wherein the phenyl moiety is substituted by one tofive R¹⁰, pyridyl-C₁-C₄alkylene- or pyridyl-C₁-C₄alkylene- wherein thepyridyl moiety is substituted by one to four R¹⁰,tetrahydrofuranyl-C₁-C₄alkylene- or tetrahydrofuranyl-C₁-C₄alkylene-wherein the tetrahydrofuranyl moiety is substituted by one to five R¹⁰,imidazolyl-C₁-C₄alkylene- or imidazolyl-C₁-C₄alkylene- wherein theimidazolyl moiety is substituted by one to three R¹⁰,pyrazolyl-C₁-C₄alkylene- or pyryazolyl-C₁-C₄alkylene- wherein thepyrazolyl moiety is substituted by one to three R¹⁰,pyrrolyl-C₁-C₄alkylene- or pyrrolyl-C₁-C₄alkylene- wherein the pyrrolylmoiety is substituted by one to four R¹⁰, thiazolyl-C₁-C₄alkylene- orthiazolyl-C₁-C₄alkylene- wherein the thiazolyl moiety is substituted byone to four R¹⁰, oxetanyl or oxetanyl substituted by one to five R¹⁰,thietanyl or thietanyl substituted by one to five R¹⁰, oxo-thietanyl oroxo-thietanyl substituted by one to five R¹⁰, or dioxo-thietanyl ordioxo-thietanyl substituted by one to five R¹⁰.

Even more preferably R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by oneto five R⁸, C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one tofive R⁹, phenyl-C₁-C₄alkylene- or phenyl-C₁-C₄alkylene- wherein thephenyl moiety is substituted by one to five R¹⁰, pyridyl-C₁-C₄alkylene-or pyridyl-C₁-C₄alkylene- wherein the pyridyl moiety is substituted byone to four R¹⁰, oxetanyl or oxetanyl substituted by one to five R¹⁰,thietanyl or thietanyl substituted by one to five R¹⁰, oxo-thietanyl oroxo-thietanyl substituted by one to five R¹⁰, dioxo-thietanyl ordioxo-thietanyl substituted by one to five R¹⁰,C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene, for example C₁-C₈alkyl orC₁-C₈alkyl substituted by one to five R⁸, C₃-C₁₀cycloalkyl orC₃-C₁₀cycloalkyl substituted by one to five R⁹, phenyl-C₁-C₄alkylene- orphenyl-C₁-C₄alkylene- wherein the phenyl moiety is substituted by one tofive R¹⁰, pyridyl-C₁-C₄alkylene- or pyridyl-C₁-C₄alkylene- wherein thepyridyl moiety is substituted by one to four R¹⁰, oxetanyl or oxetanylsubstituted by one to five R¹⁰, thietanyl or thietanyl substituted byone to five R¹⁰, oxo-thietanyl or oxo-thietanyl substituted by one tofive R¹⁰, or dioxo-thietanyl or dioxo-thietanyl substituted by one tofive R¹⁰, more preferably C₁-C₈alkyl or C₁-C₈alkyl substituted by one tothree halogen atoms, C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted byone or two methyl groups, phenyl-C₁-C₄alkylene- or phenyl-C₁-C₄alkylene-wherein the phenyl moiety is substituted by one to five R¹⁰,pyridyl-C₁-C₄alkylene- or pyridyl-C₁-C₄alkylene- wherein the pyridylmoiety is substituted by one to four R¹⁰, thietanyl, oxo-thietanyl,dioxo-thietanyl, C₁-C₈alkylaminocarbonyl-methylene,C₁-C₈haloalkylaminocarbonyl-methylene, orC₃-C₈cycloalkyl-aminocarbonyl-methylene, for example C₁-C₈alkyl orC₁-C₈alkyl substituted by one to three halogen atoms, C₃-C₁₀cycloalkylor C₃-C₁₀cycloalkyl substituted by one or two methyl groups,phenyl-C₁-C₄alkylene- or phenyl-C₁-C₄alkylene- wherein the phenyl moietyis substituted by one to four R¹⁰, pyridyl-C₁-C₄alkylene- orpyridyl-C₁-C₄alkylene- wherein the pyridyl moiety is substituted by oneto four R¹⁰, thietanyl, oxo-thietanyl or dioxo-thietanyl, mostpreferably butyl-, cyclobutyl-, 1-phenyl-eth-1-yl-, phenyl-methyl-,(pyrid-2-yl)-methyl-, thietanyl-, oxo-thietanyl- or dioxo-thietanyl-.

A group of preferred compounds are those wherein R² is C₁-C₆alkyl orC₁-C₆alkyl substituted by one to five R⁸, for example ethyl-, butyl-,but-2-yl-, 3-bromo-propyl-, 2,2,2-trifluoro-ethyl-,3,3,3-trifluoro-propyl-, 2-methoxy-ethyl-, and 1-methoxy-prop-2-yl-.

A group of preferred compounds are those wherein R² is C₃-C₈cycloalkylor C₃-C₈cycloalkyl substituted by one to five R⁹, for examplecyclobutyl-, and 2-methyl-cyclohex-1-yl-.

A group of preferred compounds are those wherein R² isaryl-C₁-C₂alkylene- or aryl-C₁-C₂alkylene- wherein the aryl moiety issubstituted by one to five R¹⁰, for example phenyl-methyl-,1-phenyl-eth-1-yl-, 2-phenyl-eth-1-yl-, (3-chloro-phenyl)-methyl-,(2-fluoro-phenyl)-methyl-, (4-methoxy-phenyl)-methyl-,(2-trifluoromethyl-phenyl)-methyl-, and(2-trifluoromethoxy-phenyl)-methyl-.

A group of preferred compounds are those wherein R² isheterocyclyl-C₁-C₂alkylene- or heterocyclyl-C₁-C₂alkylene- wherein theheterocyclyl moiety is substituted by one to five R¹⁰ in which theheterocyclyl group is selected from 1,2,3 triazolyl, 1,2,4 triazolyl,tetrazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, tetrahydrothiophenyl,isoxazolinyl, pyridyl, tetrahydrofuranyl, imidazolyl, pyrazolyl,pyrrolyl, thiazolyl, oxetanyl, thietanyl, oxo-thietanyl anddioxo-thietanyl. A group of preferred compounds are those wherein R² isheterocyclyl-C₁-C₂alkylene- or heterocyclyl-C₁-C₂alkylene- wherein theheterocyclyl moiety is substituted by one to five R¹⁰, for example(pyrid-2-yl)-methyl-, (pyrid-3-yl)-methyl-,(2-chloro-pyrid-5-yl)-methyl-, (1-methyl-1H-imidazol-4-yl)-methyl-,(furan-2-yl)-methyl-, 2-(thiophen-2′-yl)-eth-1-yl-,2-(indol-3′-yl)-eth-1-yl-, (1H-benzimidazol-2-yl)-methyl-,(oxetan-2-yl)-methyl-, (tetrahydrofuran-2-yl)-methyl-,2-([1′,3′]dioxolan-2′-yl)-eth-1-yl-, 2-(morpholin-4′-yl)-eth-1-yl-,2-(benzo[1′,3′]dioxol-5′-yl)-eth-1-yl-, and(2,3-dihydro-benzo[1,4]dioxin-6-yl)-methyl-, more preferably R² isheteroaryl-C₁-C₂alkylene- or heteroaryl-C₁-C₂alkylene- wherein theheteroaryl moiety is substituted by one to five R¹⁰. A group ofpreferred compounds are those wherein R² is aryl or aryl substituted byone to five R¹⁰, for example 2-chloro-phenyl-, 3-fluoro-phenyl-,2-methyl-phenyl-, 2-chloro-6-methyl-phenyl-, 2-trifluoromethyl-phenyl-,and 2,4-dimethoxy-phenyl-.

A group of preferred compounds are those wherein R² is heterocyclyl- orheterocyclyl substituted by one to five R¹⁰ in which the heterocyclylgroup is selected from 1,2,3 triazolyl, 1,2,4 triazolyl, tetrazolyl,pyrimidinyl, pyrazinyl, pyridazinyl, tetrahydrothiophenyl, isoxazolinyl,pyridyl, tetrahydrofuranyl, imidazolyl, pyrazolyl, pyrrolyl, thiazolyl,oxetanyl, thietanyl, oxo-thietanyl and dioxo-thietanyl.

A group of preferred compounds are those wherein R² is heterocyclyl orheterocyclyl substituted by one to five R¹⁰, for example3-methyl-pyrid-2-yl-, 1,3-dimethyl-1H-pyrazol-5-yl-,4-methyl-thiazol-2-yl-, 5-methyl-thiadiazol-2-yl-, quinolin-2-yl-,quinolin-5-yl-, benzothiazol-6-yl-, 4-methyl-benzothiazol-2-yl-,thietan-3-yl-, 1-oxo-thietan-3-yl-, 1,1-dioxo-thietan-3-yl-, and3-methyl-thietan-3-yl-, more preferably R² is oxetanyl, thietanyl,oxo-thietanyl or dioxo-thietanyl each optionally substituted by one tofive R¹⁰, most preferably R² is thietanyl, oxo-thietanyl ordioxo-thietanyl each optionally substituted by one to five R¹⁰. It isparticularly preferred that the oxetanyl, thietanyl, oxo-thietanyl ordioxo-thietanyl ring is linked via the 3-position.

A group of preferred compounds are those wherein R² is group (A).

Preferably R³ is chlorodifluoromethyl or trifluoromethyl, mostpreferably trifluoromethyl.

Preferably R⁴ is aryl or aryl substituted by one to five R¹¹, morepreferably aryl substituted by one to three R¹¹, more preferably phenylsubstituted by one to three R¹¹, even more preferably3,5-dibromo-phenyl-, 3,5-dichloro-phenyl-,3,5-bis-(trifluoromethyl)-phenyl-3,4-dichloro-phenyl-,3,4,5-trichloro-phenyl- or 3-trifluoromethyl-phenyl-, most preferably R⁴is 3,5-dichloro-phenyl.

A group of preferred compounds are those wherein R⁶ is C₁-C₈alkyl orC₁-C₈alkyl substituted by one to five R¹², aryl-C₁-C₄alkylene- oraryl-C₁-C₄alkylene- wherein the aryl moiety is substituted by one tofive R¹⁴, heteroaryl-C₁-C₄alkylene- or heteroaryl-C₁-C₄alkylene- whereinthe heteroaryl moiety is substituted by one to five R¹⁴, more preferablyC₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R¹²,phenyl-C₁-C₄alkylene- or phenyl-C₁-C₄alkylene- wherein the phenyl moietyis substituted by one to five R¹⁴, more preferably C₁-C₈alkyl orC₁-C₈alkyl substituted by one to five R¹², phenyl-methylene- orphenyl-methylene wherein the phenyl moiety is substituted by one to fiveR¹⁴, more preferably C₁-C₈alkyl or phenyl-methylene, more preferablyC₁-C₈alkyl, more preferably methyl.

A group of preferred compounds are those where R⁶ is C₁-C₄alkoxycarbonyl-, C₁-C₄ alkenyloxycarbonyl-, C₁-C₄ alkynyloxycarbonyl-,benzyloxycarbonyl- or benzyloxycarbonyl- in which the benzyl group isoptionally substituted by one to five R¹⁶, more preferably R⁶ ismethyloxycarbonyl, ethyloxycarbonyl, propyloxycarbonyl,allyloxycarbonyl, propargyloxycarbonyl, benzyloxcarbonyl orbenzyloxycarbonyl optionally substituted by one to five R¹⁶.

Preferably each R⁷ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkenyl, C₁-C₈haloalkenyl, C₁-C₈alkoxy-, orC₁-C₈haloalkoxy-, more preferably bromo, chloro, fluoro, cyano, nitro,methyl, ethyl, trifluoromethyl, vinyl, methoxy, difluoromethoxy, ortrifluoromethoxy, most preferably methyl.

Preferably each R⁸ is independently halogen, cyano, nitro, hydroxy,C₁-C₈alkoxy-, C₁-C₈haloalkoxy-, C₁-C₈alkylcarbonyl-,C₁-C₈alkoxycarbonyl-, mercapto, C₁-C₈alkylthio-, C₁-C₈haloalkylthio-,C₁-C₈alkylsulfinyl-, C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, morepreferably C₁-C₈haloalkylsulfonyl-, halogen, cyano, nitro, hydroxy,C₁-C₈alkoxy-, C₁-C₈haloalkoxy-, mercapto, C₁-C₈alkylthio-,C₁-C₈haloalkylthio-, more preferably bromo, chloro, fluoro, methoxy, ormethylthio, most preferably chloro, fluoro, or methoxy.

Preferably each R⁹ is independently halogen or C₁-C₈alkyl, morepreferably chloro, fluoro or methyl, most preferably methyl.

Preferably each R¹⁰ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy-, C₁-C₈haloalkoxy-, more preferably bromo,chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy,difluoromethoxy, or trifluoromethoxy, most preferably bromo, chloro,fluoro, cyano or methyl.

Preferably each R¹¹ is independently halogen, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy-, C₁-C₈haloalkoxy-, C₁-C₈alkylthio-, orC₁-C₈haloalkylthio-, more preferably bromo, chloro, fluoro,trifluoromethyl, methoxy, or methylthio, most preferably bromo orchloro.

Preferably each R¹² is independently halogen, cyano, nitro, hydroxy,C₁-C₈alkoxy-, C₁-C₈haloalkoxy-, mercapto, C₁-C₈alkylthio-,C₁-C₈haloalkylthio-, more preferably bromo, chloro, fluoro, methoxy, ormethylthio, most preferably chloro, fluoro, or methoxy.

Preferably each R¹³ is independently chloro, fluoro or methyl, mostpreferably methyl.

Preferably each R¹⁴ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy-, C₁-C₈haloalkoxy-, more preferably bromo,chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy,difluoromethoxy, or trifluoromethoxy, most preferably bromo, chloro,fluoro, cyano or methyl.

Preferably each R¹⁵ is independently bromo, chloro, fluoro, cyano,nitro, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, ortrifluoromethoxy, more preferably bromo, chloro, fluoro, nitro, ormethyl, most preferably chloro, fluoro, or methyl.

Preferably each R¹⁶ is independently C₁-C₄ alkyl, C₁-C₄ haloalkyl orhalogen, more preferably methyl, ethyl, halomethyl, haloethyl, fluoro,chloro or bromo.

Preferably, R¹⁷ and R¹⁸ are each independently hydrogen, halogen,C₁-C₁₂alkyl, C₁-C₁₂haloalkyl, C₃-C₈cycloalkyl, C₃-C₈halocycloalkyl,C₂-C₁₂alkenyl or C₂-C₁₂haloalkenyl, C₂-C₁₂alkynyl, C₂-C₁₂haloalkynylcyano, C₁-C₁₂alkoxycarbonyl, C₁-C₁₂haloalkoxycarbonyl,C₁-C₁₂alkoxythiocarbonyl, C₁-C₁₂haloalkoxythiocarbonyl, or R¹⁷ and R¹⁸together with the carbon atom to which they are attached may form a 3 to6-membered carbocyclic ring. More preferably, R¹⁷ and R¹⁸ are eachindependently hydrogen, halogen, cyano, C₁-C₄alkyl or C₁-C₄haloalkyl,even more preferably R¹⁷ and R¹⁸ are hydrogen, halogen or methyl, mostpreferably hydrogen.

Preferably, R¹⁹ is hydrogen, NH₂, hydroxyl, C₁-C₁₂alkoxy,C₁-C₁₂haloalkoxy, C₁-C₁₂alkylcarbonylamino, C₁-C₂haloalkylcarbonylamino,C₁-C₂alkylamino, C₁-C₁₂haloalkylamino, C₁-C₁₂alkyl, C₁-C₁₂haloalkyl,C₃-C₈cycloalkyl, C₃-C₈halocycloalkyl, cyano, C₁-C₁₂alkenyl,C₁-C₁₂haloalkenyl, C₂-C₁₂alkynyl, C₂-C₁₂haloalkynyl,C₁-C₁₂alkylcarbonyl, C₁-C₁₂haloalkylcarbonyl, C₁-C₈alkoxycarbonyl, orC₁-C₈haloalkoxycarbonyl. More preferably, R¹⁹ is hydrogen, C₁-C₈alkyl,C₁-C₈alkoxy, C₁-C₈alkylcarbonyl, or C₁-C₈alkoxycarbonyl, even morepreferably hydrogen or methyl, most preferably R¹⁹ is hydrogen.

Preferably R²⁰ is hydrogen, cyano, carbonyl, thiocarbonyl,C₁-C₁₂alkylcarbonyl, C₁-C₂haloalkylcarbonyl, C₁-C₂alkylthiocarbonyl,C₁-C₂haloalkylthiocarbonyl, C₁-C₁₂alkylaminocarbonyl,C₁-C₁₂alkylaminothiocarbonyl, C₂-C₂₄ (total carbon number)dialkylaminocarbonyl, C₂-C₂₄ (total carbon number)dialkylaminothiocarbonyl, C₁-C₁₂alkoxyaminocarbonyl,C₁-C₁₂alkoxyaminothiocarbonyl, C₁-C₁₂alkoxycarbonyl,C₁-C₁₂haloalkoxycarbonyl, C₁-C₁₂alkoxythiocarbonyl,C₁-C₁₂haloalkoxythiocarbonyl, C₁-C₁₂thioalkoxycarbonyl,C₁-C₁₂thioalkoxythiocarbonyl, C₁-C₁₂alkylsulfonyl,C₁-C₁₂haloalkylsulfonyl, C₃-C₁₂cycloalkylcarbonyl,C₃-C₁₂halocycloalkylcarbonyl, C₂-C₁₂alkenylcarbonyl,C₂-C₁₂haloalkenylcarbonyl, C₂-C₁₂ alkynylcarbonyl,C₂-C₁₂haloalkynylcarbonyl, C₃-C₁₂cycloalkyl-C₁-C₁₂alkylcarbonyl,C₃-C₁₂halocycloalkyl-C₁-C₁₂alkylcarbonyl,C₂-C₂alkylsulfenyl-C₁-C₂alkylcarbonyl,C₂-C₂haloalkylsulfenyl-C₁-C₁₂alkylcarbonyl,C₁-C₁₂alkylsulfinyl-C₁-C₁₂alkylcarbonyl,C₁-C₁₂haloalkylsulfinyl-C₁-C₁₂alkylcarbonyl,C₁-C₁₂alkylsulfonyl-C₁-C₁₂alkylcarbonyl,C₁-C₁₂haloalkylsulfonyl-C₁-C₁₂alkylcarbonyl,C₁-C₂alkylcarbonyl-C₁-C₂alkylcarbonyl,C₁-C₂haloalkylcarbonyl-C₁-C₂alkylcarbonyl,C₃-C₁₂cycloalkylaminocarbonyl, C₂-C₁₂alkenylaminocarbonyl,C₂-C₁₂alkynylaminocarbonyl or C(═O)R²¹. More preferably, R²⁰ isC₁-C₄alkylcarbonyl, C₁-C₄haloalkylcarbonyl, C₃-C₆cycloalkylcarbonyl,C₃-C₆halocycloalkylcarbonyl or C(═O)R²¹.

In one group of compounds R¹⁹ and R² together with the nitrogen atom towhich they are bound may form a 3- to 6-membered heterocyclic ring whichmay be substituted by one to five R², or may be substituted with a keto,thioketo or nitroimino group.

Preferably, R²¹ is aryl or aryl substituted by one to five R²²,heterocyclyl or heterocyclyl substituted by one to five R²²,aryl-methylene or aryl-methylene wherein the aryl moiety is substitutedby one to five R²², or heterocyclyl-methylene or heterocyclyl-methylene,preferably each aryl group is a phenyl group and each heterocyclyl groupis selected from pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl,pyrazolyl, imidazolyl, triazolyl, tetrahydrothiophenyl, tetrazolyl,furanyl, thiophenyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl,isothiazolyl, thiadiazolyl, quinolinyl, cinnolinyl, quinoxalinyl,indolyl, indazolyl, benzimidazolyl, benzothiophenyl, benzothiazolyl,oxetanyl, thietanyl, oxo-thietanyl, dioxo-thietanyl, pyrrolidinyl,tetrahydrofuranyl, [1,3]dioxolanyl, piperidinyl, piperazinyl,[1,4]dioxanyl, morpholinyl, 2,3-dihydro-benzofuranyl,benzo[1,3]dioxolanyl, and 2,3-dihydro-benzo[1,4]dioxinyl, thiazolidinyl,and 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, preferably each heterocyclylgroup is selected from thiophenyl, thiazolyl, cinnolinyl andthiazolidinyl.

Preferably each R²² is independently bromo, chloro, fluoro, cyano,nitro, oxo, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy,trifluoromethoxy, methyl-N═, methylthio, phenyl or phenyl substituted byone to three halogen, more preferably bromo, chloro, fluoro, nitro, ormethyl.

Preferably each Z is independently halogen, cyano, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy, or C₁-C₄haloalkoxy, more preferably each Zis independently hydrogen, halogen, methyl, halomethyl, methoxy orhalomethoxy.

In one group of compounds of the invention

P is P1;

A¹, A², A³ and A⁴ are independently of each other C—H, C—R⁷, ornitrogen;

G¹ is oxygen or sulfur,

R¹ is hydrogen, C₁-C₈alkyl, C₁-C₈alkoxy-, C₁-C₈alkylcarbonyl-, orC₁-C₈alkoxycarbonyl-;

R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁸,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R⁹,aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moiety issubstituted by one to five R¹⁰, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R¹⁰, aryl or aryl substituted by one to fiveR¹⁰, heterocyclyl or heterocyclyl substituted by one to five R¹⁰,C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene;R³ is C₁-C₈haloalkyl;R⁴ is aryl or aryl substituted by one to five R¹¹, or heteroaryl orheteroaryl substituted by one to five R¹¹;R⁵ is hydrogen;R⁶ is hydrogen, C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R¹²,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R¹³,aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moiety issubstituted by one to five R¹⁴, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R¹⁴, aryl or aryl substituted by one to fiveR¹⁴, or heterocyclyl or heterocyclyl substituted by one to five R¹⁴,C₁-C₄ alkoxycarbonyl-, C₁-C₄ alkenyloxycarbonyl-, C₁-C₄alkynyloxycarbonyl-, benzyloxycarbonyl- or benzyloxycarbonyl- in whichthe benzyl group is optionally substituted by one to five R¹⁶;each R⁷ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkenyl, C₁-C₈haloalkenyl, C₁-C₈alkynyl,C₁-C₈haloalkynyl, C₃-C₁₀cycloalkyl, C₁-C₈alkoxy-, C₁-C₈haloalkoxy-,C₁-C₈alkylthio-, C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-,C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, orC₁-C₈haloalkylsulfonyl-;each R⁸ and R¹² is independently halogen, cyano, nitro, hydroxy,C₁-C₈alkoxy-, C₁-C₈haloalkoxy-, C₁-C₈alkylcarbonyl-,C₁-C₈alkoxycarbonyl-, mercapto, C₁-C₈alkylthio-, C₁-C₈haloalkylthio-,C₁-C₈alkylsulfinyl-, C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, orC₁-C₈haloalkylsulfonyl-;each R⁹ and R¹³ is independently halogen or C₁-C₈alkyl;each R¹⁰, R¹¹ and R¹⁴ is independently halogen, cyano, nitro,C₁-C₈alkyl, C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl,C₂-C₈alkynyl, C₂-C₈haloalkynyl, hydroxy, C₁-C₈alkoxy-, C₁-C₈haloalkoxy-,mercapto, C₁-C₈alkylthio-, C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-,C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, C₁-C₈haloalkylsulfonyl-,C₁-C₈alkylcarbonyl-, C₁-C₈alkoxycarbonyl-, aryl or aryl substituted byone to five R¹⁵, or heterocyclyl or heterocyclyl substituted by one tofive R¹⁵;each R¹⁵ is independently halogen, cyano, nitro, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy-, or C₁-C₄haloalkoxy-;each R¹⁶ is independently halogen, cyano, formyl, C₁-C₄ alkyl, C₁-C₄haloalkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₃-C₆ cycloalkyl; or a saltor N-oxide thereof.

A group of preferred compounds are those wherein

A¹, A², A³ and A⁴ are independently of each other C—H, C—R⁷, ornitrogen;

G¹ is oxygen or sulfur,

R¹ is hydrogen, C₁-C₈alkyl, C₁-C₈alkoxy-, C₁-C₈alkylcarbonyl-, orC₁-C₈alkoxycarbonyl-;

R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁸,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R⁹,aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moiety issubstituted by one to five R¹⁰, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R¹⁰, aryl or aryl substituted by one to fiveR¹⁰, or heterocyclyl or heterocyclyl substituted by one to five R¹⁰;

R³ is C₁-C₈haloalkyl;

R⁴ is aryl or aryl substituted by one to five R¹¹, or heteroaryl orheteroaryl substituted by one to five R¹¹;

R⁵ is hydrogen;

R⁶ is hydrogen, C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R¹²,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R¹³,aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moiety issubstituted by one to five R¹⁴, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R¹⁴, aryl or aryl substituted by one to fiveR¹⁴, or heterocyclyl or heterocyclyl substituted by one to five R¹⁴;

each R⁷ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkenyl, C₁-C₈haloalkenyl, C₁-C₈alkynyl,C₁-C₈haloalkynyl, C₃-C₁₀cycloalkyl, C₁-C₈alkoxy-, C₁-C₈haloalkoxy-,C₁-C₈alkylthio-, C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-,C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, orC₁-C₈haloalkylsulfonyl-;

each R⁸ and R¹² is independently halogen, cyano, nitro, hydroxy,C₁-C₈alkoxy-, C₁-C₈haloalkoxy-, C₁-C₈alkylcarbonyl-,C₁-C₈alkoxycarbonyl-, mercapto, C₁-C₈alkylthio-, C₁-C₈haloalkylthio-,C₁-C₈alkylsulfinyl-, C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, orC₁-C₈haloalkylsulfonyl-;

each R⁹ and R¹³ is independently halogen or C₁-C₈alkyl;

each R¹⁰, R¹¹ and R¹⁴ is independently halogen, cyano, nitro,C₁-C₈alkyl, C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl,C₂-C₈alkynyl, C₂-C₈haloalkynyl, hydroxy, C₁-C₈alkoxy-, C₁-C₈haloalkoxy-,mercapto, C₁-C₈alkylthio-, C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-,C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, C₁-C₈haloalkylsulfonyl-,C₁-C₈alkylcarbonyl-, C₁-C₈alkoxycarbonyl-, aryl or aryl substituted byone to five R¹⁵, or heterocyclyl or heterocyclyl substituted by one tofive R¹⁵;

each R¹⁵ is independently halogen, cyano, nitro, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy-, or C₁-C₄haloalkoxy-.

Another group of preferred compounds are those wherein

A¹ is C—R⁷, A² is C—H, A³ is C—H or nitrogen and A⁴ is C—H or nitrogen;

G¹ is oxygen;

R¹ is hydrogen, methyl, ethyl, methylcarbonyl-, or methoxycarbonyl-;

R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁸,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R⁹,aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moiety issubstituted by one to five R¹⁰, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R¹⁰, aryl or aryl substituted by one to fiveR¹⁰, heterocyclyl or heterocyclyl substituted by one to five R¹⁰,C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene, wherein each aryl group isa phenyl group and each heterocycle group is selected from pyridyl,tetrahydrofuranyl, imidazolyl, pyrazolyl, pyrrolyl, thiazolyl, oxetanyl,thietanyl, oxo-thietanyl and dioxo-thietanyl;

R³ is C₁-C₈ haloalkyl;

R⁴ is phenyl substituted by one to three R¹¹;

R⁵ is hydrogen;

R⁶ is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R¹²,aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moiety issubstituted by one to five R¹⁴, heteroaryl-C₁-C₄alkylene- orheteroaryl-C₁-C₄alkylene- wherein the heteroaryl moiety is substitutedby one to five R¹⁴;

R⁷ is independently halogen, cyano, nitro, C₁-C₈alkyl, C₁-C₈haloalkyl,C₁-C₈alkenyl, C₁-C₈haloalkenyl, C₁-C₈alkoxy-, or C₁-C₈haloalkoxy-;

each R⁸ is independently halogen, cyano, nitro, hydroxy, C₁-C₈alkoxy-,C₁-C₈haloalkoxy-, mercapto, C₁-C₈alkylthio-, C₁-C₈haloalkylthio-;

each R⁹ is independently chloro, fluoro or methyl;

each R¹⁰ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy-, C₁-C₈haloalkoxy-;

each R¹¹ is independently halogen, C₁-C₈alkyl, C₁-C₈haloalkyl,C₁-C₈alkoxy-, C₁-C₈haloalkoxy-, C₁-C₈alkylthio-, or C₁-C₈haloalkylthio-;

each R¹² is independently halogen, cyano, nitro, hydroxy, C₁-C₈alkoxy-,C₁-C₈haloalkoxy-, mercapto, C₁-C₈alkylthio-, C₁-C₈haloalkylthio-;

each R¹⁴ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy-, C₁-C₈haloalkoxy-;

Yet another group of preferred compounds are those wherein

A¹ is C—R⁷, A² is C—H, A³ is C—H and A⁴ is C—H;

G¹ is oxygen;

R¹ is hydrogen, methyl or ethyl;

R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁸,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R⁹,phenyl-C₁-C₄alkylene- or phenyl-C₁-C₄alkylene- wherein the phenyl moietyis substituted by one to five R¹⁰, pyridyl-C₁-C₄alkylene- orpyridyl-C₁-C₄alkylene- wherein the pyridyl moiety is substituted by oneto four R¹⁰, oxetanyl or oxetanyl substituted by one to five R¹⁰,thietanyl or thietanyl substituted by one to five R¹⁰, oxo-thietanyl oroxo-thietanyl substituted by one to five R¹⁰, or dioxo-thietanyl ordioxo-thietanyl substituted by one to five R¹⁰,C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene;

R³ is chlorodifluoromethyl or trifluoromethyl;

R⁴ is 3,5-dibromo-phenyl-, 3,5-dichloro-phenyl-,3,5-bis-(trifluoromethyl)-phenyl-, 3,4-dichloro-phenyl-,3,4,5-trichloro-phenyl- or 3-trifluoromethyl-phenyl-

R⁵ is hydrogen;

R⁶ is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R¹²,phenyl-C₁-C₄alkylene- or phenyl-C₁-C₄alkylene- wherein the phenyl moietyis substituted by one to five R¹⁴,

R⁷ is independently bromo, chloro, fluoro, cyano, nitro, methyl, ethyl,trifluoromethyl, vinyl, methoxy, difluoromethoxy, or trifluoromethoxy;

each R⁸ is independently bromo, chloro, fluoro, methoxy, or methylthio;

each R⁹ is methyl;

each R¹⁰ is independently bromo, chloro, fluoro, cyano, nitro, methyl,ethyl, trifluoromethyl, methoxy, difluoromethoxy, or trifluoromethoxy;

each R¹² is independently bromo, chloro, fluoro, methoxy, or methylthio;

each R¹⁴ is independently bromo, chloro, fluoro, cyano, nitro, methyl,ethyl, trifluoromethyl, methoxy, difluoromethoxy, or trifluoromethoxy.

A further group of preferred compounds are those wherein

A¹ is C—R⁷, A² is C—H, A³ is C—H and A⁴ is C—H;

G¹ is oxygen;

R¹ is hydrogen;

R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to three halogenatoms, C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one or twomethyl groups, phenyl-C₁-C₄alkylene- or phenyl-C₁-C₄alkylene- whereinthe phenyl moiety is substituted by one to five R¹⁰,pyridyl-C₁-C₄alkylene- or pyridyl-C₁-C₄alkylene- wherein the pyridylmoiety is substituted by one to four R¹⁰, thietanyl, oxo-thietanyl ordioxo-thietanyl;

R³ is trifluoromethyl;

R⁴ is 3,5-dichloro-phenyl;

R⁵ is hydrogen;

R⁶ is C₁-C₈alkyl;

R⁷ is methyl

each R¹⁰ is independently bromo, chloro, fluoro, cyano or methyl.

A further group of preferred compounds are those wherein

A¹ is C—R⁷, A² is CH, A³ is CH and A⁴ is CH;

G¹ is oxygen;

R¹ is hydrogen;

R² is C₂-C₆alkyl or C₂-C₆alkyl substituted by one to three halogenatoms, C₄-C₈cycloalkyl or C₄-C₈cycloalkyl substituted by one or twomethyl groups, phenyl-C₁-C₂alkylene- or phenyl-C₁-C₂alkylene- whereinthe phenyl moiety is substituted by one to five R¹⁰,pyridyl-C₁-C₂alkylene- or pyridyl-C₁-C₂alkylene- wherein the pyridylmoiety is substituted by one to four R¹⁰, thietanyl, oxo-thietanyl ordioxo-thietanyl;

R³ is trifluoromethyl;

R⁴ is 3,5-dichloro-phenyl;

R⁵ is hydrogen;

R⁶ is C₁-C₈alkyl;

R⁷ is methyl

each R¹⁰ is independently bromo, chloro, fluoro, cyano or methyl.

In these groups of preferred compounds P is preferably P1.

In one embodiment the present invention provides compounds of formula(Ia)

wherein G¹, R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ are as defined for compoundsof formula (I); or a salt or N-oxide thereof. The preferences for G¹,R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ are the same as the preferences set outfor the corresponding substituents of compounds of the formula (I).

In a further embodiment the present invention provides compounds offormula (Ib)

wherein R³, R⁴, R⁵, R⁶ and R⁷ are as defined for compounds of formula(I) and Het is selected from H1 to H9 as defined for compounds offormula I; or a salt or N-oxide thereof. The preferences for R³, R⁴, R⁵,R⁶, R⁷ and Het are the same as the preferences set out for thecorresponding substituents of compounds of the formula (I).

In a further embodiment the present invention provides compounds offormula (Ic)

wherein R³, R⁴, R⁵, R⁶, R⁷, R17, R18, R¹⁹ and R²⁰ are as defined forcompounds of formula (I); or a salt or N-oxide thereof. The preferencesfor R³, R⁴, R⁵, R⁶, R⁷, R17, R18, R¹⁹ and R²⁰ are the same as thepreferences set out for the corresponding substituents of compounds ofthe formula (I).

Certain intermediates are novel and as such form a further aspect of theinvention. One group of novel intermediates are compounds of formula(Int-I)

wherein A¹, A², A³, A⁴, R³, R⁴, R⁵ and R⁶ are as defined for a compoundof formula (I), G¹ is oxygen, and R is hydroxy, C₁-C₁₆alkoxy or halogen,such as bromo, chloro or fluoro; or a salt or N-oxide thereof. Thepreferences for A¹, A², A³, A⁴, R³, R⁴. R⁵ and R⁶ are the same as thepreferences set out for the corresponding substituents of a compound offormula (I). Preferably R is hydroxy, C₁-C₆alkoxy or chloro.

A further group of novel intermediates are compounds of formula Int-II

wherein A¹, A², A³, A⁴, R³, R⁴. R⁵ and R⁶ are as defined for a compoundof formula I, and X^(B) is a leaving group, such as halogen,C₁-C₈alkoxy, C₁-C₈alkylsulfonyloxy, C₁-C₈haloalkylsulfonyloxy,C₁-C₈arylsulfonyloxy, cyano, optionally substituted C₁-C₈arylsulfonyloxy(aryl is preferably phenyl), diazonium salts (e.g. X^(B) is —N₂ ⁺Cl⁻,—N₂ ⁺BF₄ ⁻, —N₂ ⁺Br⁻, —N₂ ⁺PF₆ ⁻, phosphonate esters (e.g. —OP(O)(OR)₂,wherein R is methyl or ethyl), preferably bromo, iodo, chloro,trifluoromethylsulfoxy, p-toluenesulfoxy, diazonium chloride; or a saltor N-oxide thereof. The preferences for A¹, A², A³, A⁴, R³, R⁴. R⁵ andR⁶ are the same as the preferences set out for the correspondingsubstituents of a compound of formula (I).

A further group of novel intermediates are compounds of formula Int-III

wherein A¹, A², A³, A⁴, R³, R⁴, R⁵, R⁶, R¹⁷ and R¹⁸ are as defined for acompound of formula I, Q is phthalimidyl, hydroxy, or a leaving groupsuch as halogen, C₁-C₈alkoxy, C₁-C₈alkylsulfonyloxy,C₁-C₈haloalkylsulfonyloxy, C₁-C₈arylsulfonyloxy, optionally substitutedC₁-C₈arylsulfonyloxy (aryl is preferably phenyl), diazonium salts (e.g.X^(B) is —N₂ ⁺Cl⁻, —N₂ ⁺ BF₄ ⁻, —N₂ ⁺Br⁻, —N₂ ⁺PF₆ ⁻), phosphonateesters (e.g. —OP(O)(OR)₂, wherein R is methyl or to ethyl), preferablybromo, iodo, chloro, trifluoromethylsulfoxy, p-toluenesulfoxy, diazoniumchloride; or a salt or N-oxide thereof. The preferences for A¹, A², A³,A⁴, R³, R⁴. R⁵, R⁶, R¹⁷ and R¹⁸ are the same as the preferences set outfor the corresponding substituents of a compound of formula (I).

The compounds in Table 1 and 2 below illustrate the compounds of theinvention.

TABLE 1 Table 1 provides 117 compounds of formula (Ia) wherein G¹ isoxygen, R³ is trifluoromethyl, R⁴ is 3,5-dichloro-phenyl-, R⁵ ishydrogen, R⁶ and R⁷ are both methyl, and R¹ and R² have the valueslisted in the table below. (Ia)

Compound numbers R¹ R² 1.01 H ethyl- 1.02 H butyl- 1.03 H but-2-yl- 1.04H 3-bromo-propyl- 1.05 H 2,2,2-trifluoro-ethyl- 1.06 H3,3,3-trifluoro-propyl- 1.07 H 2-methoxy-ethyl- 1.08 H1-methoxy-prop-2-yl- 1.09 H cyclobutyl- 1.10 H 2-methyl-cyclohex-1-yl-1.11 H phenyl-methyl- 1.12 H 1-phenyl-eth-1-yl- 1.13 H2-phenyl-eth-1-yl- 1.14 H (3-chloro-phenyl)-methyl- 1.15 H(2-fluoro-phenyl)-methyl- 1.16 H (4-methoxy-phenyl)-methyl- 1.17 H(2-trifluoromethyl-phenyl)-methyl- 1.18 H(2-trifluoromethoxy-phenyl)-methyl- 1.19 H (pyrid-2-yl)-methyl- 1.20 H(pyrid-3 -yl)-methyl- 1.21 H (2-chloro-pyrid-5-yl)-methyl- 1.22 H(1-methyl-1H-imidazol-4-yl)-methyl- 1.23 H (furan-2-yl)-methyl- 1.24 H2-(thiophen-2′-yl)-eth-1-yl- 1.25 H 2-(indol-3′-yl)-eth-1-yl- 1.26 H(1H-benzimidazol-2-yl)-methyl- 1.27 H (oxetan-2-yl)-methyl- 1.28 H(tetrahydrofuran-2-yl)-methyl- 1.29 H 2-([1′,3]dioxolan-2′-yl)-eth-1-yl-1.30 H 2-(morpholin-4′-yl)-eth-1-yl- 1.31 H2-(benzo[1′,3′]dioxol-5′-yl)-eth-1-yl- 1.32 H(2,3-dihydro-benzo[1,4]dioxin-6-yl)-methyl- 1.33 H 2-chloro-phenyl- 1.34H 3-fluoro-phenyl- 1.35 H 2-methyl-phenyl- 1.36 H2-chloro-6-methyl-phenyl- 1.37 H 2-trifluoromethyl-phenyl- 1.38 H2,4-dimethoxy-phenyl- 1.39 H 3-methyl-pyrid-2-yl- 1.40 H1,3-dimethyl-1H-pyrazol-5-yl- 1.41 H 4-methyl-thiazol-2-yl- 1.42 H5-methyl-thiadiazol-2-yl- 1.43 H quinolin-2-yl- 1.44 H quinolin-5-yl-1.45 H benzothiazol-6-yl- 1.46 H 4-methyl-benzothiazol-2-yl- 1.47 Hthietan-3-yl- 1.48 H 1-oxo-thietan-3-yl- 1.49 H 1,1-dioxo-thietan-3-yl-1.50 H 3-methyl-thietan-3-yl- 1.51 HN-(2,2,2-Trifluoro-ethyl)-acetamide-2-yl 1.52 H thietan-2-yl-methyl-1.53 H 1-oxo-thietan-2-yl-methyl- 1.54 H 1,1-dioxo-thietan-2-yl-methyl-1.55 H thietan-3-yl-methyl- 1.56 H 1-oxo-thietan-3-yl-methyl- 1.57 H1,1-dioxo-thietan-3-yl-methyl- 1.58 H thietan-3-yl-ethyl- 1.59 H1-oxo-thietan-3-yl-ethyl- 1.60 H 1,1-dioxo-thietan-3-yl-ethyl- 1.61 H2-fluoro-cyclopropyl 1.62 H n-Butyl 1.63 H 2-Methoxy-1-methyl-ethyl 1.64H 1-Oxo-thietan-3-yl 1.65 H 2-ethyl-isoxazolidin-3-one-4-yl 1.66 HDihydro-thiophen-2-one-3-yl 1.67 H 6-Ethoxycarbonyl-cyclohex-3-enyl 1.68H 2-Benzylsulfanyl-ethyl 1.69 H 4-Methanesulfonyl-benzyl 1.70 HN′,N′-Dimethylamino-ethyl 1.71 H sec-Butyl 1.72 H Butan-1-ol-2-yl 1.73 H2,2-Difluoro-ethyl 1.74 H Ethynyl-cyclohexyl 1.75 H2-Morpholin-4-yl-ethyl 1.76 H 3-Pyrrolidin-1-yl-propyl 1.77 H3-Piperidin-1-yl-propyl 1.78 H[3-(4-Chloro-phenyl)-isoxazol-5-yl]-methyl 1.79 H Phenethyl 1.80 H1,2,2,6,6-Pentamethyl-piperidin-4-yl 1.81 H 2-Phenoxy-ethyl 1.82 H3-Chloro-benzyl 1.83 H 2-Acetylamino-ethyl 1.84 H 4-Pyrazol-1-yl-benzyl1.85 H 2-Methylsulfanyl-ethyl 1.86 H 2-Piperidin-1-yl-benzyl 1.87 H4-Phenoxy-benzyl 1.88 H (6-Chloro-pyridin-3-yl)-methyl 1.89 H1-Benzyl-pyrrolidin-3-yl 1.90 H 2-(4-Benzyl-piperazin-1-yl)-ethyl 1.91 HFuran-2-yl-methyl 1.92 H 1H-Indazol-5-yl 1.93 H 4-Pyrrol-1-yl-phenyl1.94 H 4-Piperidin-1-yl-phenyl 1.95 H 2-Methylsulfanyl-phenyl 1.96 H4-Methyl-2-oxo-2H-chromen-7-yl 1.97 H 4-Dimethylsulfamoyl-phenyl 1.98 H2,5-Dimethyl-2H-pyrazol-3-yl 1.99 H5-Methylsulfanyl-1H-[1,2,4]triazol-3-yl 1.100 H4-Hydroxy-6-methyl-pyrimidin-2-yl 1.101 H Quinolin-2-yl 1.102 H5-Methyl-3-phenyl-isoxazol-4-yl 1.103 H 9H-Purin-6-yl 1.104 H5-Acetyl-4-methyl-thiazol-2-yl 1.105 H 4-Methyl-benzothiazol-2-yl 1.106H 5-Methyl-[1,3,4]thiadiazol-2-yl 1.107 H 4,6-Dimethyl-2H-pyrazolo[3,4-b]pyridin-3-yl 1.108 H3-(2,2,2-Trifluoro-ethoxyimino)-cyclobutyl 1.109 H 2-Thietan-3-yl-ethyl1.110 H 2-(1,1-Dioxo-thietan-3-yl)-ethyl 1.112 H3-Oxo-2-(2,2,2-trifluoro-ethyl)-isoxazolidin-4-yl 1.113 H

1.114 H

1.115 H 2-(2,2,2-trifluoro-ethyl)-isoxazolidin-3-one-4-yl 1.116 H2-(2,2-Difluoro-ethyl)-isoxazolidin-3-one-4-yl 1.117 H2-(2-Fluoro-ethyl)-isoxazolidin-3-one-4-yl

TABLE 2 Table 2 provides 180 compounds of formula (Id) wherein R³ istrifluoromethyl, R⁵ is hydrogen, R⁶ is methyl, and R⁴, R⁷ and P have thevalues listed in the table below. (Id)

No. R⁴ R⁷ P 1 3,5-dichloro-phenyl CN

2 3,5-dichloro-phenyl CN

3 3,5-dichloro-phenyl CN

4 3,5-dichloro-phenyl CN

5 3,5-dichloro-phenyl H

6 3,5-dichloro-phenyl H

7 3,5-dichloro-phenyl Cl

8 3,5-dichloro-phenyl Cl

9 3,5-dichloro-phenyl Cl

10 3,5-dichloro-phenyl Cl

11 3,5-dichloro-phenyl Cl

12 3,5-dichloro-phenyl Cl

13 3,5-dichloro-phenyl Cl

14 3,5-dichloro-phenyl Cl

15 3,5-dichloro-phenyl Br

16 3,5-dichloro-phenyl Br

17 3,5-dichloro-phenyl Br

18 3,5-dichloro-phenyl Br

19 3,5-dichloro-phenyl Br

20 3,5-dichloro-phenyl Br

21 3,5-dichloro-phenyl Br

22 3,5-dichloro-phenyl Br

23 3,5-dichloro-phenyl CF₃

24 3,5-dichloro-phenyl CF₃

25 3,5-dichloro-phenyl CF₃

26 3,5-dichloro-phenyl CF₃

27 3,5-dichloro-phenyl CF₃

28 3,5-dichloro-phenyl CF₃

29 3,5-dichloro-phenyl CF₃

30 3,5-dichloro-phenyl CF₃

31 3,5-Bis trifluoro methyl-phenyl CN

32 3,5-Bis trifluoro methyl-phenyl CN

33 3,5-Bis trifluoro methyl-phenyl CN

34 3,5-Bis trifluoro methyl-phenyl CN

35 3,5-Bis trifluoro methyl-phenyl H

36 3,5-Bis trifluoro methyl-phenyl H

37 3,5-Bis trifluoro methyl-phenyl Cl

38 3,5-Bis trifluoro methyl-phenyl Cl

39 3,5-Bis trifluoro methyl-phenyl Cl

40 3,5-Bis trifluoro methyl-phenyl Cl

41 3,5-Bis trifluoro methyl-phenyl Cl

42 3,5-Bis trifluoro methyl-phenyl Cl

43 3,5-Bis trifluoro methyl-phenyl Cl

44 3,5-Bis trifluoro methyl-phenyl Cl

45 3,5-Bis trifluoro methyl-phenyl Br

46 3,5-Bis trifluoro methyl-phenyl Br

47 3,5-Bis trifluoro methyl-phenyl Br

48 3,5-Bis trifluoro methyl-phenyl Br

49 3,5-Bis trifluoro methyl-phenyl Br

50 3,5-Bis trifluoro methyl-phenyl Br

51 3,5-Bis trifluoro methyl-phenyl Br

52 3,5-Bis trifluoro methyl-phenyl Br

53 3,5-Bis trifluoro methyl-phenyl CF₃

54 3,5-Bis trifluoro methyl-phenyl CF₃

55 3,5-Bis trifluoro methyl-phenyl CF₃

56 3,5-Bis trifluoro methyl-phenyl CF₃

57 3,5-Bis trifluoro methyl-phenyl CF₃

58 3,5-Bis trifluoro methyl-phenyl CF₃

59 3,5-Bis trifluoro methyl-phenyl CF₃

60 3,5-Bis trifluoro methyl-phenyl CF₃

61 3,4,5-Trichloro-phenyl CN

62 3,4,5-Trichloro-phenyl CN

63 3,4,5-Trichloro-phenyl CN

64 3,4,5-Trichloro-phenyl CN

65 3,4,5-Trichloro-phenyl H

66 3,4,5-Trichloro-phenyl H

67 3,4,5-Trichloro-phenyl Cl

68 3,4,5-Trichloro-phenyl Cl

69 3,4,5-Trichloro-phenyl Cl

70 3,4,5-Trichloro-phenyl Cl

71 3,4,5-Trichloro-phenyl Cl

72 3,4,5-Trichloro-phenyl Cl

73 3,4,5-Trichloro-phenyl Cl

74 3,4,5-Trichloro-phenyl Cl

75 3,4,5-Trichloro-phenyl Br

76 3,4,5-Trichloro-phenyl Br

77 3,4,5-Trichloro-phenyl Br

78 3,4,5-Trichloro-phenyl Br

79 3,4,5-Trichloro-phenyl Br

80 3,4,5-Trichloro-phenyl Br

81 3,4,5-Trichloro-phenyl Br

82 3,4,5-Trichloro-phenyl Br

83 3,4,5-Trichloro-phenyl CF₃

84 3,4,5-Trichloro-phenyl CF₃

85 3,4,5-Trichloro-phenyl CF₃

86 3,4,5-Trichloro-phenyl CF₃

87 3,4,5-Trichloro-phenyl CF₃

88 3,4,5-Trichloro-phenyl CF₃

89 3,4,5-Trichloro-phenyl CF₃

90 3,4,5-Trichloro-phenyl CF₃

91 3,5-dichloro-4-fluoro- phenyl CN

92 3,5-dichloro-4-fluoro- phenyl CN

93 3,5-dichloro-4-fluoro- phenyl CN

94 3,5-dichloro-4-fluoro- phenyl CN

95 3,5-dichloro-4-fluoro- phenyl H

96 3,5-dichloro-4-fluoro- phenyl H

97 3,5-dichloro-4-fluoro- phenyl Cl

98 3,5-dichloro-4-fluoro- phenyl Cl

99 3,5-dichloro-4-fluoro- phenyl Cl

100 3,5-dichloro-4-fluoro- phenyl Cl

101 3,5-dichloro-4-fluoro- phenyl Cl

102 3,5-dichloro-4-fluoro- phenyl Cl

103 3,5-dichloro-4-fluoro- phenyl Cl

104 3,5-dichloro-4-fluoro- phenyl Cl

105 3,5-dichloro-4-fluoro- phenyl Br

106 3,5-dichloro-4-fluoro- phenyl Br

107 3,5-dichloro-4-fluoro- phenyl Br

108 3,5-dichloro-4-fluoro- phenyl Br

109 3,5-dichloro-4-fluoro- phenyl Br

110 3,5-dichloro-4-fluoro- phenyl Br

111 3,5-dichloro-4-fluoro- phenyl Br

112 3,5-dichloro-4-fluoro- phenyl Br

113 3,5-dichloro-4-fluoro- phenyl CF₃

114 3,5-dichloro-4-fluoro- phenyl CF₃

115 3,5-dichloro-4-fluoro- phenyl CF₃

116 3,5-dichloro-4-fluoro- phenyl CF₃

117 3,5-dichloro-4-fluoro- phenyl CF₃

118 3,5-dichloro-4-fluoro- phenyl CF₃

119 3,5-dichloro-4-fluoro- phenyl CF₃

120 3,5-dichloro-4-fluoro- phenyl CF₃

121 3-chloro-5-trifluoro methyl-phenyl CN

122 3-chloro-5-trifluoro methyl-phenyl CN

123 3-chloro-5-trifluoro methyl-phenyl CN

124 3-chloro-5-trifluoro methyl-phenyl CN

125 3-chloro-5-trifluoro methyl-phenyl H

126 3-chloro-5-trifluoro methyl-phenyl H

127 3-chloro-5-trifluoro methyl-phenyl Cl

128 3-chloro-5-trifluoro methyl-phenyl Cl

129 3-chloro-5-trifluoro methyl-phenyl Cl

130 3-chloro-5-trifluoro methyl-phenyl Cl

131 3-chloro-5-trifluoro methyl-phenyl Cl

132 3-chloro-5-trifluoro methyl-phenyl Cl

133 3-chloro-5-trifluoro methyl-phenyl Cl

134 3-chloro-5-trifluoro methyl-phenyl Cl

135 3-chloro-5-trifluoro methyl-phenyl Br

136 3-chloro-5-trifluoro methyl-phenyl Br

137 3-chloro-5-trifluoro methyl-phenyl Br

138 3-chloro-5-trifluoro methyl-phenyl Br

139 3-chloro-5-trifluoro methyl-phenyl Br

140 3-chloro-5-trifluoro methyl-phenyl Br

141 3-chloro-5-trifluoro methyl-phenyl Br

142 3-chloro-5-trifluoro methyl-phenyl Br

143 3-chloro-5-trifluoro methyl-phenyl CF₃

144 3-chloro-5-trifluoro methyl-phenyl CF₃

145 3-chloro-5-trifluoro methyl-phenyl CF₃

146 3-chloro-5-trifluoro methyl-phenyl CF₃

147 3-chloro-5-trifluoro methyl-phenyl CF₃

148 3-chloro-5-trifluoro methyl-phenyl CF₃

149 3-chloro-5-trifluoro methyl-phenyl CF₃

150 3-chloro-5-trifluoro methyl-phenyl CF₃

151 3-chloro-5-bromo-phenyl CN

152 3-chloro-5-bromo-phenyl CN

153 3-chloro-5-bromo-phenyl CN

154 3-chloro-5-bromo-phenyl CN

155 3-chloro-5-bromo-phenyl H

156 3-chloro-5-bromo-phenyl H

157 3-chloro-5-bromo-phenyl Cl

158 3-chloro-5-bromo-phenyl Cl

159 3-chloro-5-bromo-phenyl Cl

160 3-chloro-5-bromo-phenyl Cl

161 3-chloro-5-bromo-phenyl Cl

162 3-chloro-5-bromo-phenyl Cl

163 3-chloro-5-bromo-phenyl Cl

164 3-chloro-5-bromo-phenyl Cl

165 3-chloro-5-bromo-phenyl Br

166 3-chloro-5-bromo-phenyl Br

167 3-chloro-5-bromo-phenyl Br

168 3-chloro-5-bromo-phenyl Br

169 3-chloro-5-bromo-phenyl Br

170 3-chloro-5-bromo-phenyl Br

171 3-chloro-5-bromo-phenyl Br

172 3-chloro-5-bromo-phenyl Br

173 3-chloro-5-bromo-phenyl CF₃

174 3-chloro-5-bromo-phenyl CF₃

175 3-chloro-5-bromo-phenyl CF₃

176 3-chloro-5-bromo-phenyl CF₃

177 3-chloro-5-bromo-phenyl CF₃

178 3-chloro-5-bromo-phenyl CF₃

179 3-chloro-5-bromo-phenyl CF₃

180 3-chloro-5-bromo-phenyl CF₃

Compounds of formula I include at least one chiral centre and may existas compounds of formula I* or compounds of formula I**.

Compounds of formula I*:

Generally compounds of formula I** are more biologically active thancompounds of formula I*. The invention includes mixtures of compounds I*and I** in any ratio e.g. in a molar ratio of 1:99 to 99:1, e.g. 10:1 to1:10, e.g. a substantially 50:50 molar ratio. In an enantiomerically (orepimerically) enriched mixture of formula I**, the molar proportion ofcompound I** compared to the total amount of both enantiomers is forexample greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90,95, 96, 97, 98, or at least 99%. Likewise, in enantiomerically (orepimerically) enriched mixture of formula I*, the molar proportion ofthe compound of formula I* compared to the total amount of bothenantiomers (or epimerically) is for example greater than 50%, e.g. atleast 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%.Enantiomerically (or epimerically) enriched mixtures of formula I** arepreferred.

The compounds of the invention may be made by a variety of methods asshown in Schemes 1 to 21.

1) Compounds of formula (IA), wherein R⁶ is other than hydrogen, can bemade by treatment of a compound of formula (XVI) with base, such aslithium diisopropylamine (“LDA”), followed by the addition of a compound(XII) wherein X, is a leaving group, for example an alkylating or anacylating agent, in the presence of a suitable solvent, such astetrahydrofuran. Suitable alkylating agents are, for example, alkylhalides, such as methyl iodide (Me-I), for making a compound (IA) whereR⁶ is C₁-C₈alkyl, in particular allyl, and acylating agents such asmethyl chloroformate, ethyl chloroformate for making a compound (IA)where R⁶ is methoxycarbonyl or ethoxycarbonyl. The reaction is carriedout at a temperature of from −120° C. to +30° C., preferably from −100°C. to 0° C. Alternatively, compounds of formula (I), wherein R⁶ is otherthan hydrogen, can be made by treatment of a compound of formula (XVI)with a strong alkylating agent, such as trimethyloxoniumtetrafluoroborate, in a suitable solvent, for instance1,2-dichloroethane.

2) Compounds of formula (IA) can be made by treatment of a compound offormula (II) with a compound of formula (X) and a dehydrating reagent.Alternatively, carboxylic acid (IA) is transformed to an an activatedderivative, such as an acid chloride, for instance by treatment withthionyl chloride, or a mixed anhydride, for instance by treatment withethyl chloroformate, and the activated derivative is reacted with acompound of formula (X), optionally in the presence of a base, and in asuitable solvent, such as, for instance, tetrahydrofuran. The reactionis carried out at a temperature of from −120° C. to +130° C., preferablyfrom −100° C. to 100° C.

3) Compounds of formula (II), wherein G¹ is oxygen, can be made bytreatment of a compound of formula (III), wherein X is a halogen, forinstance bromine, with a metallating agent, such as a metal, forinstance magnesium, or an organometallic compound, for instancebutyllithium, followed by the treatment with carbon dioxide. Thereaction is carried out at a temperature of from −120° C. to +130° C.,preferably from −100° C. to 100° C.

4) Compounds of formula (III), wherein R⁶ is other than hydrogen, can bemade by treatment of a compound of formula (XIII) with base, such aslithium diisopropylamine (“LDA”), followed by the addition of a compound(XII) wherein X, is a leaving group, for example an alkylating or anacylating agent, in the presence of a suitable solvent, such astetrahydrofuran. Suitable alkylating agents are, for example, alkylhalides, such as methyl iodide (Me-I), for making a compound (III) whereR⁶ is C₁-C₈alkyl, in particular allyl, and acylating agents such asmethyl chloroformate, ethyl chloroformate for making a compound (III)where R⁶ is methoxycarbonyl or ethoxycarbonyl. The reaction is carriedout at a temperature of from −120° C. to +30° C., preferably from −100°C. to 0° C. Alternatively, compounds of formula (III), wherein R⁶ isother than hydrogen, can be made by treatment of a compound of formula(XIII) with a strong alkylating agent, such as trimethyloxoniumtetrafluoroborate, in a suitable solvent, for instance1,2-dichloroethane.

5) Compounds of formula (III), wherein X^(B) is a leaving group, e.g. ahalogen, for instance bromine, can be made by treatment of a compound offormula (IV), wherein X^(B) is a leaving group, e.g. a halogen, forinstance bromine, with a compound of the formula (IX) in a suitablesolvent, for instance ethanol. Instead of a compound of the formula(IX), a salt of a compound of the formula (IX), for instance ahydrochloride, can be used for this transformation, in which case thereaction can be carried out in the presence of a base, such as an aminebase, for instance triethylamine. The reaction is carried out at atemperature of from −120° C. to +130° C., preferably from −100° C. to100° C.

6) Compounds of formula (II), wherein G¹ is oxygen, can be made byhydrolysis of a compound of formula (VIII), wherein G¹ is oxygen, andR_(x) is C₁-C₆alkyl, such as methyl or tert-butyl. For instance, in thecase where R_(x) is methyl or ethyl, the hydrolysis can be done withwater and a base, such as potassium hydroxide, in the absence or in thepresence of a solvent, such as, for instance, tetrahydrofurane ormethynol. In the case where R_(x) is, for example, tert-butyl, thehydrolysis is done in the presence of acid, such as trifluoroacetic acidor hydrochloric acid. The reaction is carried out at a temperature offrom −120° C. to +130° C., preferably from −100° C. to 100° C.

7) Compounds of formula (VIII) wherein R⁶ is other than hydrogen,wherein G¹ is oxygen and R_(x) is C₁-C₆alkyl, such as methyl ortert-butyl, can be prepared by reaction of an isoxazoline of formula(XI) wherein G¹ is oxygen and R_(x) is C₁-C₆alkyl, such as methyl ortert-butyl, with a base and a compound (XII) wherein X, is a leavinggroup, for example an alkylating or an acylating agent, in the presenceof a suitable solvent, such as tetrahydrofuran. Suitable alkylatingagents are, for example, alkyl halides, such as methyl iodide (Me-I),for making a compound (VIII) where R⁶ is C₁-C₈alkyl, in particularallyl, and acylating agents such as methyl chloroformate, ethylchloroformate for making a compound (VIII) where R⁶ is methoxycarbonylor ethoxycarbonyl. The reaction is carried out at a temperature of from−120° C. to +30° C., preferably from −100° C. to 0° C.

8) Compounds of formula (VIII) can be made by treatment of a compound offormula (XVII) with a compound of the formula (IX) in a suitablesolvent, for instance ethanol. Instead of a compound of the formula(IX), a salt of a compound of the formula (IX), for instance ahydrochloride, can be used for this transformation, in which case thereaction can be carried out in the presence of a base, such as an aminebase, for instance triethylamine. The reaction is carried out at atemperature of from −120° C. to +130° C., preferably from −100° C. to100° C.

9) Compounds of formula (XVII), wherein G¹ is oxygen and R_(x) isC₁-C₆alkyl, such as, for example, ethyl, can be made by treatment of acompound of formula (IV), wherein X^(B) is a leaving group, e.g. ahalogen, for instance bromine, with a catalyst, such as a palladiumcatalyst, for instance PdCl₂(PPh₃)₂, and a compound of the formula (XV),wherein R_(x) is C₁-C₆alkyl, such as, for example, ethyl. Optionally,the reaction is carried out in the presence of a base, such as, forexample, triethylamine. The reaction is carried out under an atmosphereof carbon monoxide, at a pressure of 1 to 200 bar, preferably at 10 to100 bar. The reaction is carried out at a temperature of from −20° C. to+230° C., preferably from 0° C. to 200° C.

10) Compounds of formula (IV) can be made by treatment of a compound offormula (XIV) with a compound of the formula (VI) in a suitable solvent,for instance N,N-dimethylformamide or dichloromethane, in the presenceof a base, such as, for example, calcium hydroxide, potassium carbonateor triethylamine. The reaction is carried out at a temperature of from−120° C. to +130° C., preferably from −100° C. to 100° C.

11) Alternatively, compounds of formula (IV) can be made by treatment ofa compound of formula (V) with a compound of the formula (VI) in asuitable solvent, for instance toluene. The reaction is carried out at atemperature of from −120° C. to +230° C., preferably from 0° C. to 150°C.

12) Compounds of formula (V) can be made by treatment of a compound offormula (VII) with triphenylphosphine in a suitable solvent, forinstance dichloromethane, followed by treatment of the intermediatephosphonium salt with a base, such as, for example, sodium bicarbonate.The reaction is carried out at a temperature of from −120° C. to +130°C., preferably from −100° C. to 100° C.

13) Compounds of formula (IB), wherein P is P2, R¹⁹ is as defined aboveand R² is different from H, can be made by treatment of compounds(XVIII) with a compound (XIX), wherein X, is a leaving group, forexample an acylating agent, in the presence of a suitable solvent, suchas tetrahydrofuran, optionally in the presence of a base, such astriethylamine. Suitable acylating agents are, for example, carboxylicacid chlorides such as acetyl chloride, for making a compound (I) whereR²⁰ is acetyl. Further acylating agents are, for example, carboxylicacid anhydrides, or carboxylic acids in the presence of couplingreagents, which are known to the persons skilled in the art. Thereaction is carried out at a temperature of from −120° C. to +130° C.,preferably from −50° C. to 50° C.

14) Compounds of the formula (XVIII), wherein P is P2 and R¹⁹ and R²⁰are hydrogen, can be made, for example, by treatment of compounds of theformula (XX) with hydrazine, or with acid, or with base. The reaction iscarried out at a temperature of from −120° C. to +130° C., preferablyfrom 0° C. to 100° C.

15) Compounds of the formula (XX) can be made, for example, by treatmentof compounds of the formula (XXI) with potassium phthalimide, or withphthalimide and a suitable base. In formula (XXI), X_(a) is a leavinggroup, a halogen for example, such as chlorine. The reaction is carriedout at a temperature of from −120° C. to +130° C., preferably from −50°C. to 50° C.

16) Compounds of the formula (XXI) can be prepared, for example, when Xais Cl, by treatment of compounds (XXII) with thionyl chloride, or, inthe case when Xa is Br, by treatment of compounds (XXII) with PBr₃ orwith triphenylphosphine and CBr₄. Further such transformations are knownto the person skilled in the art. The reaction is carried out at atemperature of from −120° C. to +130° C., preferably from −0° C. to 100°C.

17) Compounds of the formula (XXII), wherein R¹⁷ and R¹⁸ are H, can beprepared, for example, by treatment of compounds of formula (VIII),wherein G¹ is oxygen and R_(x) is C₁-C₆alkyl, such as, for example,ethyl, with a reducing agent, such as, for example, sodium borohydride.The reaction is carried out at a temperature of from −120° C. to +130°C., preferably from −0° C. to 100° C.

18) Compounds of formula (I), wherein P is P1, P2 or an optionallysubstituted heterocycle, can be made by treatment of a compound offormula (XXIII) with a compound of the formula (IX) in a suitablesolvent, for instance ethanol. Instead of a compound of the formula(IX), a salt of a compound of the formula (IX), for instance ahydrochloride, can be used for this transformation, in which case thereaction can be carried out in the presence of a base, such as an aminebase, for instance triethylamine. The reaction is carried out at atemperature of from −120° C. to +130° C., preferably from −100° C. to100° C.

19) Compounds of formula (XXIV), wherein Pn is an optionally substitutedheterocycle, can be made, for example in the case where the heterocycleis attached via a nitrogen atom, by treatment of a compound (IV) whereinX is a halogen, such as fluorine, with a heterocyclic compound Pn-H anda suitable base, such as potassium carbonate. Alternatively, compoundsof formula (XXIV), wherein Pn is an optionally substituted heterocycle,can be made, for example in the case where the heterocycle is attachedvia a carbon atom, by treatment of a compound (IV) wherein X is ahalogen, such as bromine, with a heterocyclic compound Pn-M, wherein Mis hydrogen or a metal, such as boron, magnesium or zink, in which caseM can be optionally substituted, with a base and a suitable catalyst,such as a palladium or a copper catalyst, in the presence of a suitableligand for the catalyst, such as, for example, a diamine ligand, or aphosphine ligand. Such reactions are carried out at a temperature offrom −120° C. to +130° C., preferably from −100° C. to 100° C.

20) Compounds of formula (IC), wherein P is P2 or a heterocycle can beprepared similarly to compounds of formula (IA) in scheme 2.

Compounds of formula (I) contain a chiral centre giving rise toenantiomers of the formula (I*) and (I**).

Enantiomerically enriched mixtures of compounds of formula (I*) or (I**)may be prepared, for example, according to schemes 1, 6 or 9 byformation of intermediate III or VIII via an asymmetric cyclization withan N-substituted hydroxylamine. Examples for the cyclization of enoneswith N-substituted hydroxylamine are described in the literature, suchas in Tetrahedron Letters (1975), (34), 2979-80, and references citedtherein. Alternatively, such enantiomerically enriched mixtures may beprepared according to schemes 1, 2, 5, 8 or 21 by N-alkylation ofenantiomerically enriched mixtures of intermediate XI, XIII, XVI or XXV.N-alkylations of isoxazolines are described, for example, in Farmaco(2005), 60(11-12), 948-954, and references cited therein.Enantiomerically enriched mixtures of intermediates XI, XIII, XVI andXXV can be prepared, for example, in analogy to methods described in theliterature, such as, for example, in WO 2009/063910 A1, and referencescited therein.

The compounds of formula (I) can be used to control infestations ofinsect pests such as Lepidoptera, Diptera, Hemiptera, Thysanoptera,Orthoptera, Dictyoptera, Coleoptera, Siphonaptera, Hymenoptera andIsoptera and also other invertebrate pests, for example, acarine,nematode and mollusc pests. Insects, acarines, nematodes and molluscsare hereinafter collectively referred to as pests. The pests which maybe controlled by the use of the invention compounds include those pestsassociated with agriculture (which term includes the growing of cropsfor food and fiber products), horticulture and animal husbandry,companion animals, forestry and the storage of products of vegetableorigin (such as fruit, grain and timber); those pests associated withthe damage of man-made structures and the transmission of diseases ofman and animals; and also nuisance pests (such as flies).

The compounds of the invention may be used for example on turf,ornamentals, such as flowers, shrubs, broad-leaved trees or evergreens,for example conifers, as well as for tree injection, pest management andthe like.

Examples of pest species which may be controlled by the compounds offormula (I) include: Myzus persicae (aphid), Aphis gossypii (aphid),Aphis fabae (aphid), Lygus spp. (capsids), Dysdercus spp. (capsids),Nilaparvata lugens (planthopper), Nephotettixc incticeps (leafhopper),Nezara spp. (stinkbugs), Euschistus spp. (stinkbugs), Leptocorisa spp.(stinkbugs), Frankliniella occidentalis (thrip), Thrips spp. (thrips),Leptinotarsa decemlineata (Colorado potato beetle), Anthonomus grandis(boll weevil), Aonidiella spp. (scale insects), Trialeurodes spp. (whiteflies), Bemisia tabaci (white fly), Ostrinia nubilalis (European cornborer), Spodoptera littoralis (cotton leafworm), Heliothis virescens(tobacco budworm), Helicoverpa armigera (cotton bollworm), Helicoverpazea (cotton bollworm), Sylepta derogata (cotton leaf roller), Pierisbrassicae (white butterfly), Plutella xylostella (diamond back moth),Agrotis spp. (cutworms), Chilo suppressalis (rice stem borer), Locustamigratoria (locust), Chortiocetes terminifera (locust), Diabrotica spp.(rootworms), Panonychus ulmi (European red mite), Panonychus citri(citrus red mite), Tetranychus urticae (two-spotted spider mite),Tetranychus cinnabarinus (carmine spider mite), Phyllocoptruta oleivora(citrus rust mite), Polyphagotarsonemus latus (broad mite), Brevipalpusspp. (flat mites), Boophilus microplus (cattle tick), Dermacentorvariabilis (American dog tick), Ctenocephalidesfelis (cat flea),Liriomyza spp. (leafminer), Musca domestica (housefly), Aedes aegypti(mosquito), Anopheles spp. (mosquitoes), Culex spp. (mosquitoes),Lucillia spp. (blowflies), Blattella germanica (cockroach), Periplanetaamericana (cockroach), Blatta orientalis (cockroach), termites of theMastotermitidae (for example Mastotermes spp.), the Kalotermitidae (forexample Neotermes spp.), the Rhinotermitidae (for example Coptotermesformosanus, Reticulitermes flavipes, R. speratu, R. virginicus, R.hesperus, and R. santonensis) and the Termitidae (for exampleGlobitermes sulfureus), Solenopsis geminata (fire ant), Monomoriumpharaonis (pharaoh's ant), Damalinia spp. and Linognathus spp. (bitingand sucking lice), Meloidogyne spp. (root knot nematodes), Globoderaspp. and Heterodera spp. (cyst nematodes), Pratylenchus spp. (lesionnematodes), Rhodopholus spp. (banana burrowing nematodes), Tylenchulusspp. (citrus nematodes), Haemonchus contortus (barber pole worm),Caenorhabditis elegans (vinegar eelworm), Trichostrongylus spp. (gastrointestinal nematodes) and Deroceras reticulatum (slug).

The invention therefore provides a method of controlling insects,acarines, nematodes or molluscs which comprises applying aninsecticidally, acaricidally, nematicidally or molluscicidally effectiveamount of a compound of formula (I), or a composition containing acompound of formula (I), to a pest, a locus of pest, preferably a plant,or to a plant susceptible to attack by a pest. The compounds of formula(I) are preferably used against insects or acarines.

The term “plant” as used herein includes seedlings, bushes and trees.

Crops are to be understood as also including those crops which have beenrendered tolerant to herbicides or classes of herbicides (e.g. ALS-,GS-, EPSPS-, PPO- and HPPD-inhibitors) by conventional methods ofbreeding or by genetic engineering. An example of a crop that has beenrendered tolerant to imidazolinones, e.g. imazamox, by conventionalmethods of breeding is Clearfield® summer rape (canola). Examples ofcrops that have been rendered tolerant to herbicides by geneticengineering methods include e.g. glyphosate- and glufosinate-resistantmaize varieties commercially available under the trade namesRoundupReady® and LibertyLink®.

Crops are also to be understood as being those which have been renderedresistant to harmful insects by genetic engineering methods, for exampleBt maize (resistant to European corn borer), Bt cotton (resistant tocotton boll weevil) and also Bt potatoes (resistant to Colorado beetle).Examples of Bt maize are the Bt 176 maize hybrids of NK® (SyngentaSeeds). Examples of transgenic plants comprising one or more genes thatcode for an insecticidal resistance and express one or more toxins areKnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard®(cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®.

Plant crops or seed material thereof can be both resistant to herbicidesand, at the same time, resistant to insect feeding (“stacked” transgenicevents). For example, seed can have the ability to express aninsecticidal Cry3 protein while at the same time being tolerant toglyphosate.

Crops are also to be understood as being those which are obtained byconventional methods of breeding or genetic engineering and containso-called output traits (e.g. improved storage stability, highernutritional value and improved flavor).

In order to apply a compound of formula (I) as an insecticide,acaricide, nematicide or molluscicide to a pest, a locus of pest, or toa plant susceptible to attack by a pest, a compound of formula (I) isusually formulated into a composition which includes, in addition to thecompound of formula (I), a suitable inert diluent or carrier and,optionally, a surface active agent (SFA). SFAs are chemicals which areable to modify the properties of an interface (for example,liquid/solid, liquid/air or liquid/liquid interfaces) by lowering theinterfacial tension and thereby leading to changes in other properties(for example dispersion, emulsification and wetting). It is preferredthat all compositions (both solid and liquid formulations) comprise, byweight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to 60%,of a compound of formula (I). The composition is generally used for thecontrol of pests such that a compound of formula (I) is applied at arate of from 0.1 g to 10 kg per hectare, preferably from 1 g to 6 kg perhectare, more preferably from 1 g to 1 kg per hectare.

When used in a seed dressing, a compound of formula (I) is used at arate of 0.0001 g to 10 g (for example 0.001 g or 0.05 g), preferably0.005 g to 10 g, more preferably 0.005 g to 4 g, per kilogram of seed.

In another aspect the present invention provides an insecticidal,acaricidal, nematicidal or molluscicidal composition comprising aninsecticidally, acaricidally, nematicidally or molluscicidally effectiveamount of a compound of formula (I) and a suitable carrier or diluenttherefor. The composition is preferably an insecticidal or acaricidalcomposition.

The compositions can be chosen from a number of formulation types,including dustable powders (DP), soluble powders (SP), water solublegranules (SG), water dispersible granules (WG), wettable powders (WP),granules (GR) (slow or fast release), soluble concentrates (SL), oilmiscible liquids (OL), ultra low volume liquids (UL), emulsifiableconcentrates (EC), dispersible concentrates (DC), emulsions (both oil inwater (EW) and water in oil (EO)), micro-emulsions (ME), suspensionconcentrates (SC), aerosols, fogging/smoke formulations, capsulesuspensions (CS) and seed treatment formulations. The formulation typechosen in any instance will depend upon the particular purpose envisagedand the physical, chemical and biological properties of the compound offormula (I).

Dustable powders (DP) may be prepared by mixing a compound of formula(I) with one or more solid diluents (for example natural clays, kaolin,pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk,diatomaceous earths, calcium phosphates, calcium and magnesiumcarbonates, sulfur, lime, flours, talc and other organic and inorganicsolid carriers) and mechanically grinding the mixture to a fine powder.

Soluble powders (SP) may be prepared by mixing a compound of formula (I)with one or more water-soluble inorganic salts (such as sodiumbicarbonate, sodium carbonate or magnesium sulfate) or one or morewater-soluble organic solids (such as a polysaccharide) and, optionally,one or more wetting agents, one or more dispersing agents or a mixtureof said agents to improve water dispersibility/solubility. The mixtureis then ground to a fine powder. Similar compositions may also begranulated to form water soluble granules (SG).

Wettable powders (WP) may be prepared by mixing a compound of formula(I) with one or more solid diluents or carriers, one or more wettingagents and, preferably, one or more dispersing agents and, optionally,one or more suspending agents to facilitate the dispersion in liquids.The mixture is then ground to a fine powder. Similar compositions mayalso be granulated to form water dispersible granules (WG).

Granules (GR) may be formed either by granulating a mixture of acompound of formula (I) and one or more powdered solid diluents orcarriers, or from pre-formed blank granules by absorbing a compound offormula (I) (or a solution thereof, in a suitable agent) in a porousgranular material (such as pumice, attapulgite clays, fuller's earth,kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing acompound of formula (I) (or a solution thereof, in a suitable agent) onto a hard core material (such as sands, silicates, mineral carbonates,sulfates or phosphates) and drying if necessary. Agents which arecommonly used to aid absorption or adsorption include solvents (such asaliphatic and aromatic petroleum solvents, alcohols, ethers, ketones andesters) and sticking agents (such as polyvinyl acetates, polyvinylalcohols, dextrins, sugars and vegetable oils). One or more otheradditives may also be included in granules (for example an emulsifyingagent, wetting agent or dispersing agent).

Dispersible Concentrates (DC) may be prepared by dissolving a compoundof formula (I) in water or an organic solvent, such as a ketone, alcoholor glycol ether. These solutions may contain a surface active agent (forexample to improve water dilution or prevent crystallization in a spraytank).

Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may beprepared by dissolving a compound of formula (I) in an organic solvent(optionally containing one or more wetting agents, one or moreemulsifying agents or a mixture of said agents). Suitable organicsolvents for use in ECs include aromatic hydrocarbons (such asalkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100,SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark),ketones (such as cyclohexanone or methylcyclohexanone) and alcohols(such as benzyl alcohol, furfuryl alcohol or butanol),N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone),dimethyl amides of fatty acids (such as C₈-C₁₀ fatty acid dimethylamide)and chlorinated hydrocarbons. An EC product may spontaneously emulsifyon addition to water, to produce an emulsion with sufficient stabilityto allow spray application through appropriate equipment. Preparation ofan EW involves obtaining a compound of formula (I) either as a liquid(if it is not a liquid at room temperature, it may be melted at areasonable temperature, typically below 70° C.) or in solution (bydissolving it in an appropriate solvent) and then emulsifying theresultant liquid or solution into water containing one or more SFAs,under high shear, to produce an emulsion. Suitable solvents for use inEWs include vegetable oils, chlorinated hydrocarbons (such aschlorobenzenes), aromatic solvents (such as alkylbenzenes oralkylnaphthalenes) and other appropriate organic solvents which have alow solubility in water.

Microemulsions (ME) may be prepared by mixing water with a blend of oneor more solvents with one or more SFAs, to produce spontaneously athermodynamically stable isotropic liquid formulation. A compound offormula (I) is present initially in either the water or the solvent/SFAblend. Suitable solvents for use in MEs include those hereinbeforedescribed for use in ECs or in EWs. An ME may be either an oil-in-wateror a water-in-oil system (which system is present may be determined byconductivity measurements) and may be suitable for mixing water-solubleand oil-soluble pesticides in the same formulation. An ME is suitablefor dilution into water, either remaining as a microemulsion or forminga conventional oil-in-water emulsion.

Suspension concentrates (SC) may comprise aqueous or non-aqueoussuspensions of finely divided insoluble solid particles of a compound offormula (I). SCs may be prepared by ball or bead milling the solidcompound of formula (I) in a suitable medium, optionally with one ormore dispersing agents, to produce a fine particle suspension of thecompound. One or more wetting agents may be included in the compositionand a suspending agent may be included to reduce the rate at which theparticles settle. Alternatively, a compound of formula (I) may be drymilled and added to water, containing agents hereinbefore described, toproduce the desired end product.

Aerosol formulations comprise a compound of formula (I) and a suitablepropellant (for example n-butane). A compound of formula (I) may also bedissolved or dispersed in a suitable medium (for example water or awater miscible liquid, such as n-propanol) to provide compositions foruse in non-pressurized, hand-actuated spray pumps.

A compound of formula (I) may be mixed in the dry state with apyrotechnic mixture to form a composition suitable for generating, in anenclosed space, a smoke containing the compound.

Capsule suspensions (CS) may be prepared in a manner similar to thepreparation of EW formulations but with an additional polymerizationstage such that an aqueous dispersion of oil droplets is obtained, inwhich each oil droplet is encapsulated by a polymeric shell and containsa compound of formula (I) and, optionally, a carrier or diluenttherefor. The polymeric shell may be produced by either an interfacialpolycondensation reaction or by a coacervation procedure. Thecompositions may provide for controlled release of the compound offormula (I) and they may be used for seed treatment A compound offormula (I) may also be formulated in a biodegradable polymeric matrixto provide a slow, controlled release of the compound.

A composition may include one or more additives to improve thebiological performance of the composition (for example by improvingwetting, retention or distribution on surfaces; resistance to rain ontreated surfaces; or uptake or mobility of a compound of formula (I)).Such additives include surface active agents, spray additives based onoils, for example certain mineral oils or natural plant oils (such assoy bean and rape seed oil), and blends of these with otherbio-enhancing adjuvants (ingredients which may aid or modify the actionof a compound of formula (I)).

A compound of formula (I) may also be formulated for use as a seedtreatment, for example as a powder composition, including a powder fordry seed treatment (DS), a water soluble powder (SS) or a waterdispersible powder for slurry treatment (WS), or as a liquidcomposition, including a flowable concentrate (FS), a solution (LS) or acapsule suspension (CS). The preparations of DS, SS, WS, FS and LScompositions are very similar to those of, respectively, DP, SP, WP, SCand DC compositions described above. Compositions for treating seed mayinclude an agent for assisting the adhesion of the composition to theseed (for example a mineral oil or a film-forming barrier).

Wetting agents, dispersing agents and emulsifying agents may be surfaceSFAs of the cationic, anionic, amphoteric or non-ionic type.

Suitable SFAs of the cationic type include quaternary ammonium compounds(for example cetyltrimethyl ammonium bromide), imidazolines and aminesalts.

Suitable anionic SFAs include alkali metals salts of fatty acids, saltsof aliphatic monoesters of sulfuric acid (for example sodium laurylsulfate), salts of sulfonated aromatic compounds (for example sodiumdodecylbenzenesulfonate, calcium dodecylbenzenesulfonate,butylnaphthalene sulfonate and mixtures of sodium di-isopropyl- andtri-isopropyl-naphthalene sulfonates), ether sulfates, alcohol ethersulfates (for example sodium laureth-3-sulfate), ether carboxylates (forexample sodium laureth-3-carboxylate), phosphate esters (products fromthe reaction between one or more fatty alcohols and phosphoric acid(predominately mono-esters) or phosphorus pentoxide (predominatelydi-esters), for example the reaction between lauryl alcohol andtetraphosphoric acid; additionally these products may be ethoxylated),sulfosuccinamates, paraffin or olefine sulfonates, taurates andlignosulfonates.

Suitable SFAs of the amphoteric type include betaines, propionates andglycinates.

Suitable SFAs of the non-ionic type include condensation products ofalkylene oxides, such as ethylene oxide, propylene oxide, butylene oxideor mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetylalcohol) or with alkylphenols (such as octylphenol, nonylphenol oroctylcresol); partial esters derived from long chain fatty acids orhexitol anhydrides; condensation products of said partial esters withethylene oxide; block polymers (comprising ethylene oxide and propyleneoxide); alkanolamides; simple esters (for example fatty acidpolyethylene glycol esters); amine oxides (for example lauryl dimethylamine oxide); and lecithins.

Suitable suspending agents include hydrophilic colloids (such aspolysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose)and swelling clays (such as bentonite or attapulgite).

A compound of formula (I) may be applied by any of the known means ofapplying pesticidal compounds. For example, it may be applied,formulated or unformulated, to the pests or to a locus of the pests(such as a habitat of the pests, or a growing plant liable toinfestation by the pests) or to any part of the plant, including thefoliage, stems, branches or roots, to the seed before it is planted orto other media in which plants are growing or are to be planted (such assoil surrounding the roots, the soil generally, paddy water orhydroponic culture systems), directly or it may be sprayed on, dustedon, applied by dipping, applied as a cream or paste formulation, appliedas a vapor or applied through distribution or incorporation of acomposition (such as a granular composition or a composition packed in awater-soluble bag) in soil or an aqueous environment.

A compound of formula (I) may also be injected into plants or sprayedonto vegetation using electrodynamic spraying techniques or other lowvolume methods, or applied by land or aerial irrigation systems.

Compositions for use as aqueous preparations (aqueous solutions ordispersions) are generally supplied in the form of a concentratecontaining a high proportion of the active ingredient, the concentratebeing added to water before use. These concentrates, which may includeDCs, SCs, ECs, EWs, MEs, SGs, SPs, WPs, WGs and CSs, are often requiredto withstand storage for prolonged periods and, after such storage, tobe capable of addition to water to form aqueous preparations whichremain homogeneous for a sufficient time to enable them to be applied byconventional spray equipment. Such aqueous preparations may containvarying amounts of a compound of formula (I) (for example 0.0001 to 10%,by weight) depending upon the purpose for which they are to be used.

A compound of formula (I) may be used in mixtures with fertilizers (forexample nitrogen-, potassium- or phosphorus-containing fertilizers).Suitable formulation types include granules of fertilizer. The mixturespreferably contain up to 25% by weight of the compound of formula (I).

The invention therefore also provides a fertilizer compositioncomprising a fertilizer and a compound of formula (I).

The compositions of this invention may contain other compounds havingbiological activity, for example micronutrients or compounds havingfungicidal activity or which possess plant growth regulating,herbicidal, insecticidal, nematicidal or acaricidal activity.

The compound of formula (I) may be the sole active ingredient of thecomposition or it may be admixed with one or more additional activeingredients such as a pesticide, fungicide, synergist, herbicide orplant growth regulator where appropriate. An additional activeingredient may: provide a composition having a broader spectrum ofactivity or increased persistence at a locus; synergize the activity orcomplement the activity (for example by increasing the speed of effector overcoming repellency) of the compound of formula (I); or help toovercome or prevent the development of resistance to individualcomponents. The particular additional active ingredient will depend uponthe intended utility of the composition. Examples of suitable pesticidesinclude the following:

a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate,esfenvalerate, deltamethrin, cyhalothrin (in particularlambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin,fish safe pyrethroids (for example ethofenprox), natural pyrethrin,tetramethrin, S-bioallethrin, fenfluthrin, prallethrin or5-benzyl-3-furylmethyl-(E)-(1R,3S)-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate;b) Organophosphates, such as profenofos, sulprofos, acephate, methylparathion, azinphos-methyl, demeton-s-methyl, heptenophos, thiometon,fenamiphos, monocrotophos, profenofos, triazophos, methamidophos,dimethoate, phosphamidon, malathion, chlorpyrifos, phosalone, terbufos,fensulfothion, fonofos, phorate, phoxim, pirimiphos-methyl,pirimiphos-ethyl, fenitrothion, fosthiazate or diazinon;c) Carbamates (including aryl carbamates), such as pirimicarb,triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb,aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur,methomyl or oxamyl;d) Benzoyl ureas, such as diflubenzuron, triflumuron, hexaflumuron,flufenoxuron or chlorfluazuron;e) Organic tin compounds, such as cyhexatin, fenbutatin oxide orazocyclotin;f) Pyrazoles, such as tebufenpyrad and fenpyroximate;g) Macrolides, such as avermectins or milbemycins, for exampleabamectin, emamectin benzoate, ivermectin, milbemycin, spinosad,azadirachtin or spinetoram;h) Hormones or pheromones;i) Organochlorine compounds, such as endosulfan (in particularalpha-endosulfan), benzene hexachloride, DDT, chlordane or dieldrin;j) Amidines, such as chlordimeform or amitraz;k) Fumigant agents, such as chloropicrin, dichloropropane, methylbromide or metam;l) Neonicotinoid compounds, such as imidacloprid, thiacloprid,acetamiprid, nitenpyram, dinotefuran, thiamethoxam, clothianidin,nithiazine or flonicamid;m) Diacylhydrazines, such as tebufenozide, chromafenozide ormethoxyfenozide;n) Diphenyl ethers, such as diofenolan or pyriproxifen;o) Indoxacarb;p) Chlorfenapyr,q) Pymetrozine;r) Spirotetramat, spirodiclofen or spiromesifen;s) Diamides, such as flubendiamide, chlorantraniliprole orcyantraniliprole;t) Sulfoxaflor;u) Metaflumizone;v) Fipronil and Ethiprole;w) Pyrifluqinazonx) buprofezin; ory)4-[(6-Chloro-pyridin-3-ylmethyl)-(2,2-difluoro-ethyl)-amino]-5H-furan-2-one(DE 102006015467).

In addition to the major chemical classes of pesticide listed above,other pesticides having particular targets may be employed in thecomposition, if appropriate for the intended utility of the composition.For instance, selective insecticides for particular crops, for examplestemborer specific insecticides (such as cartap) or hopper specificinsecticides (such as buprofezin) for use in rice may be employed.Alternatively insecticides or acaricides specific for particular insectspecies/stages may also be included in the compositions (for exampleacaricidal ovo-larvicides, such as clofentezine, flubenzimine,hexythiazox or tetradifon; acaricidal motilicides, such as dicofol orpropargite; acaricides, such as bromopropylate or chlorobenzilate; orgrowth regulators, such as hydramethylnon, cyromazine, methoprene,chlorfluazuron or diflubenzuron).

Examples of fungicidal compounds which may be included in thecomposition of the invention are(E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy-iminoacetamide(SSF-129),4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole-1-sulfonamide,α-[N-(3-chloro-2,6-xylyl)-2-methoxyacetamido]-γ-butyrolactone,4-chloro-2-cyano-N,N-dimethyl-5-p-tolylimidazole-1-sulfonamide (IKF-916,cyamidazosulfamid),

3-5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide(RH-7281, zoxamide),N-allyl-4,5,-dimethyl-2-trimethylsilylthiophene-3-carboxamide(MON65500),N-(1-cyano-1,2-dimethylpropyl)-2-(2,4-dichlorophenoxy)propionamide(AC382042), N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide,acibenzolar (CGA245704), alanycarb, aldimorph, anilazine, azaconazole,azoxystrobin, benalaxyl, benomyl, biloxazol, bitertanol, blasticidin S,bromuconazole, bupirimate, captafol, captan, carbendazim, carbendazimchlorhydrate, caioxin, carpropamid, carvone, CGA41396, CGA41397,chinomethionate, chlorothalonil, chlorozolinate, clozylacon, coppercontaining compounds such as copper oxychloride, copper oxyquinolate,copper sulfate, copper tallate and Bordeaux mixture, cymoxanil,cyproconazole, cyprodinil, debacarb, di-2-pyridyl disulfide1,1′-dioxide, dichlofluanid, diclomezine, dicloran, diethofencarb,difenoconazole, difenzoquat, diflumetorim, O,O-di-iso-propyl-5-benzylthiophosphate, dimefluazole, dimetconazole, dimethomorph, dimethirimol,diniconazole, dinocap, dithianon, dodecyl dimethyl ammonium chloride,dodemorph, dodine, doguadine, edifenphos, epoxiconazole, ethirimol,ethyl-(Z)—N-benzyl-N-([methyl(methyl-thioethylideneamino-oxycarbonyl)amino]thio)-β-alaninate,etridiazole, famoxadone, fenamidone (RPA407213), fenarimol,fenbuconazole, fenfuram, fenhexamid (KBR2738), fenpiclonil, fenpropidin,fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone,fluazinam, fludioxonil, flumetover, fluoroimide, fluquinconazole,flusilazole, flutolanil, flutriafol, folpet, fuberidazole, furalaxyl,furametpyr, guazatine, hexaconazole, hydroxyisoxazole, hymexazole,imazalil, imibenconazole, iminoctadine, iminoctadine triacetate,ipconazole, iprobenfos, iprodione, iprovalicarb (SZX0722), isopropanylbutyl carbamate, isoprothiolane, kasugamycin, kresoxim-methyl, LY186054,LY211795, LY248908, mancozeb, maneb, mefenoxam, mepanipyrim, mepronil,metalaxyl, metconazole, metiram, metiram-zinc, metominostrobin,myclobutanil, neoasozin, nickel dimethyldithiocarbamate,nitrothal-iso-propyl, nuarimol, ofurace, organomercury compounds,oxadixyl, oxasulfuron, oxolinic acid, oxpoconazole, oxycarboxin,pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-A1,phosphorus acids, phthalide, picoxystrobin (ZA1963), polyoxin D,polyram, probenazole, prochloraz, procymidone, propamocarb,propiconazole, propineb, propionic acid, pyrazophos, pyrifenox,pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammoniumcompounds, quinomethionate, quinoxyfen, quintozene, sipconazole (F-155),sodium pentachlorophenate, spiroxamine, streptomycin, sulfur,tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole,thifluzamid, 2-(thiocyanomethylthio)benzothiazole, thiophanate-methyl,thiram, timibenconazole, tolclofos-methyl, tolylfluanid, triadimefon,triadimenol, triazbutil, triazoxide, tricyclazole, tridemorph,trifloxystrobin (CGA279202), triforine, triflumizole, triticonazole,validamycin A, vapam, vinclozolin, zineb, ziram;1,3-Dimethyl-1H-pyrazole-4-carboxylic acid(4′-methylsulfanyl-biphenyl-2-yl)-amide,1,3-Dimethyl-1H-pyrazole-4-carboxylic acid(2-dichloromethylene-3-ethyl-1-methyl-indan-4-yl)-amide, and1,3-Dimethyl-4H-pyrazole-4-carboxylic acid[2-(2,4-dichloro-phenyl)-2-methoxy-1-methyl-ethyl]-amide. The compoundsof formula (I) may be mixed with soil, peat or other rooting media forthe protection of plants against seed-borne, soil-borne or foliar fungaldiseases.

Examples of suitable synergists for use in the compositions includepiperonyl butoxide, sesamex, safroxan and dodecyl imidazole.

Suitable herbicides and plant-growth regulators for inclusion in thecompositions will depend upon the intended target and the effectrequired.

An example of a rice selective herbicide which may be included ispropanil. An example of a plant growth regulator for use in cotton isPIX™.

Some mixtures may comprise active ingredients which have significantlydifferent physical, chemical or biological properties such that they donot easily lend themselves to the same conventional formulation type. Inthese circumstances other formulation types may be prepared. Forexample, where one active ingredient is a water insoluble solid and theother a water insoluble liquid, it may nevertheless be possible todisperse each active ingredient in the same continuous aqueous phase bydispersing the solid active ingredient as a suspension (using apreparation analogous to that of an SC) but dispersing the liquid activeingredient as an emulsion (using a preparation analogous to that of anEW). The resultant composition is a suspoemulsion (SE) formulation.

The compounds of the invention are also useful in the field of animalhealth, e.g. they may be used against parasitic invertebrate pests, morepreferably against parasitic invertebrate pests in or on an animal.Examples of pests include nematodes, trematodes, cestodes, flies, mites,tricks, lice, fleas, true bugs and maggots. The animal may be anon-human animal, e.g. an animal associated with agriculture, e.g. acow, a pig, a sheep, a goat, a horse, or a donkey, or a companionanimal, e.g. a dog or a cat.

In a further aspect the invention provides a compound of the inventionfor use in a method of therapeutic treatment.

In a further aspect the invention relates to a method of controllingparasitic invertebrate pests in or on an animal comprising administeringa pesticidally effective amount of a compound of the invention. Theadministration may be for example oral administration, parenteraladministration or external administration, e.g. to the surface of theanimal body. In a further aspect the invention relates to a compound ofthe invention for controlling parasitic invertebrate pests in or on ananimal. In a further aspect the invention relates to use of a compoundof the invention in the manufacture of a medicament for controllingparasitic invertebrate pests in or on an animal

In a further aspect, the invention relates to a method of controllingparasitic invertebrate pests comprising administering a pesticidallyeffective amount of a compound of the invention to the environment inwhich an animal resides.

In a further aspect the invention relates to a method of protecting ananimal from a parasitic invertebrate pest comprising administering tothe animal a pesticidally effective amount of a compound of theinvention. In a further aspect the invention relates to a compound ofthe invention for use in protecting an animal from a parasiticinvertebrate pest. In a further aspect the invention relates to use of acompound of the invention in the manufacture of a medicament forprotecting an animal from a parasitic invertebrate pest.

In a further aspect the invention provides a method of treating ananimal suffering from a parasitic invertebrate pest comprisingadministering to the animal a pesticidally effective amount of acompound of the invention. In a further aspect the invention relates toa compound of the invention for use in treating an animal suffering froma parasitic invertebrate pest. In a further aspect the invention relatesto use of a compound of the invention in the manufacture of a medicamentfor treating an animal suffering from a parasitic invertebrate pest.

In a further aspect, the invention provides a pharmaceutical compositioncomprising a compound of the invention and a pharmaceutically suitableexcipient.

The compounds of the invention may be used alone or in combination withone or more other biologically active ingredients.

In one aspect the invention provides a combination product comprising apesticidally effective amount of a component A and a pesticidallyeffective amount of component B wherein component A is a compound of theinvention and component B is a compound as described below.

The compounds of the invention may be used in combination withanthelmintic agents. Such anthelmintic agents include, compoundsselected from the macrocyclic lactone class of compounds such asivermectin, avermectin, abamectin, emamectin, eprinomectin, doramectin,selamectin, moxidectin, nemadectin and milbemycin derivatives asdescribed in EP-357460, EP-444964 and EP-594291. Additional anthelminticagents include semisynthetic and biosynthetic avermectin/milbemycinderivatives such as those described in U.S. Pat. No. 5,015,630,WO-9415944 and WO-9522552. Additional anthelmintic agents include thebenzimidazoles such as albendazole, cambendazole, fenbendazole,flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, andother members of the class. Additional anthelmintic agents includeimidazothiazoles and tetrahydropyrimidines such as tetramisole,levamisole, pyrantel pamoate, oxantel or morantel. Additionalanthelmintic agents include flukicides, such as triclabendazole andclorsulon and the cestocides, such as praziquantel and epsiprantel.

The compounds of the invention may be used in combination withderivatives and analogues of the paraherquamide/marcfortine class ofanthelmintic agents, as well as the antiparasitic oxazolines such asthose disclosed in U.S. Pat. No. 5,478,855, U.S. Pat. No. 4,639,771 andDE-19520936.

The compounds of the invention may be used in combination withderivatives and analogues of the general class of dioxomorpholineantiparasitic agents as described in WO-9615121 and also withanthelmintic active cyclic depsipeptides such as those described inWO-9611945, WO-9319053, WO-9325543, EP-626375, EP-382173, WO-9419334,EP-382173, and EP-503538.

The compounds of the invention may be used in combination with otherectoparasiticides; for example, fipronil; pyrethroids; organophosphates;insect growth regulators such as lufenuron; ecdysone agonists such astebufenozide and the like; neonicotinoids such as imidacloprid and thelike.

The compounds of the invention may be used in combination with terpenealkaloids, for example those described in International PatentApplication Publication Numbers WO95/19363 or WO04/72086, particularlythe compounds disclosed therein.

Other examples of such biologically active compounds that the compoundsof the invention may be used in combination with include but are notrestricted to the following:

Organophosphates: acephate, azamethiphos, azinphos-ethyl,azinphos-methyl, bromophos, bromophos-ethyl, cadusafos, chlorethoxyphos,chlorpyrifos, chlorfenvinphos, chlormephos, demeton, demeton-S-methyl,demeton-S-methyl sulphone, dialifos, diazinon, dichlorvos, dicrotophos,dimethoate, disulfoton, ethion, ethoprophos, etrimfos, famphur,fenamiphos, fenitrothion, fensulfothion, fenthion, flupyrazofos,fonofos, formothion, fosthiazate, heptenophos, isazophos, isothioate,isoxathion, malathion, methacriphos, methamidophos, methidathion,methyl-parathion, mevinphos, monocrotophos, naled, omethoate,oxydemeton-methyl, paraoxon, parathion, parathion-methyl, phenthoate,phosalone, phosfolan, phosphocarb, phosmet, phosphamidon, phorate,phoxim, pirimiphos, pirimiphos-methyl, profenofos, propaphos,proetamphos, prothiofos, pyraclofos, pyridapenthion, quinalphos,sulprophos, temephos, terbufos, tebupirimfos, tetrachlorvinphos,thimeton, triazophos, trichlorfon, vamidothion.

Carbamates: alanycarb, aldicarb, 2-sec-butylphenyl methylcarbamate,benfuracarb, carbaryl, carbofuran, carbosulfan, cloethocarb,ethiofencarb, fenoxycarb, fenthiocarb, to furathiocarb, HCN-801,isoprocarb, indoxacarb, methiocarb, methomyl,5-methyl-m-cumenylbutyryl(methyl)carbamate, oxamyl, pirimicarb,propoxur, thiodicarb, thiofanox, triazamate, UC-51717.

Pyrethroids: acrinathin, allethrin, alphametrin, 5-benzyl-3-furylmethyl(E)-(1R)-cis-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate,bifenthrin, beta-cyfluthrin, cyfluthrin, a-cypermethrin,beta-cypermethrin, bioallethrin, bioallethrin((S)-cyclopentylisomer),bioresmethrin, bifenthrin, NCI-85193, cycloprothrin, cyhalothrin,cythithrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate,ethofenprox, fenfluthrin, fenpropathrin, fenvalerate, flucythrinate,flumethrin, fluvalinate (D isomer), imiprothrin, cyhalothrin,lambda-cyhalothrin, permethrin, phenothrin, prallethrin, pyrethrins(natural products), resmethrin, tetramethrin, transfluthrin,theta-cypermethrin, silafluofen, t-fluvalinate, tefluthrin,tralomethrin, Zeta-cypermethrin.

Arthropod growth regulators: a) chitin synthesis inhibitors:benzoylureas: chlorfluazuron, diflubenzuron, fluazuron, flucycloxuron,flufenoxuron, hexaflumuron, lufenuron, novaluron, teflubenzuron,triflumuron, buprofezin, diofenolan, hexythiazox, etoxazole,chlorfentazine; b) ecdysone antagonists: halofenozide, methoxyfenozide,tebufenozide; c) juvenoids: pyriproxyfen, methoprene (includingS-methoprene), fenoxycarb; d) lipid biosynthesis inhibitors:spirodiclofen.

Other antiparasitics: acequinocyl, amitraz, AKD-1022, ANS-118,azadirachtin, Bacillus thuringiensis, bensultap, bifenazate, binapacryl,bromopropylate, BTG-504, BTG-505, camphechlor, cartap, chlorobenzilate,chlordimeform, chlorfenapyr, chromafenozide, clothianidine, cyromazine,diacloden, diafenthiuron, DBI-3204, dinactin,dihydroxymethyldihydroxypyrrolidine, dinobuton, dinocap, endosulfan,ethiprole, ethofenprox, fenazaquin, flumite, MTI-800, fenpyroximate,fluacrypyrim, flubenzimine, flubrocythrinate, flufenzine, flufenprox,fluproxyfen, halofenprox, hydramethylnon, IKI-220, kanemite, NC-196,neem guard, nidinorterfuran, nitenpyram, SD-35651, WL-108477, pirydaryl,propargite, protrifenbute, pymethrozine, pyridaben, pyrimidifen,NC-1111, R-195, RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601,silafluofen, silomadine, spinosad, tebufenpyrad, tetradifon,tetranactin, thiacloprid, thiocyclam, thiamethoxam, tolfenpyrad,triazamate, triethoxyspinosyn, trinactin, verbutin, vertalec, YI-5301.

Fungicides: acibenzolar, aldimorph, ampropylfos, andoprim, azaconazole,azoxystrobin, benalaxyl, benomyl, bialaphos, blasticidin-S, Bordeauxmixture, bromuconazole, bupirimate, carpropamid, captafol, captan,carbendazim, chlorfenazole, chloroneb, chloropicrin, chlorothalonil,chlozolinate, copper oxychloride, copper salts, cyflufenamid, cymoxanil,cyproconazole, cyprodinil, cyprofuram, RH-7281, diclocymet,diclobutrazole, diclomezine, dicloran, difenoconazole, RP-407213,dimethomorph, domoxystrobin, diniconazole, diniconazole-M, dodine,edifenphos, epoxiconazole, famoxadone, fenamidone, fenarimol,fenbuconazole, fencaramid, fenpiclonil, fenpropidin, fenpropimorph,fentin acetate, fluazinam, fludioxonil, flumetover, flumorf/flumorlin,fentin hydroxide, fluoxastrobin, fluquinconazole, flusilazole,flutolanil, flutriafol, folpet, fosetyl-aluminium, furalaxyl,furametapyr, hexaconazole, ipconazole, iprobenfos, iprodione,isoprothiolane, kasugamycin, krsoxim-methyl, mancozeb, maneb, mefenoxam,mepronil, metalaxyl, metconazole, metominostrobin/fenominostrobin,metrafenone, myclobutanil, neoasozin, nicobifen, orysastrobin, oxadixyl,penconazole, pencycuron, probenazole, prochloraz, propamocarb,propioconazole, proquinazid, prothioconazole, pyrifenox, pyraclostrobin,pyrimethanil, pyroquilon, quinoxyfen, spiroxamine, sulfur, tebuconazole,tetrconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram,tiadinil, triadimefon, triadimenol, tricyclazole, trifloxystrobin,triticonazole, validamycin, vinclozin.

Biological agents: Bacillus thuringiensis ssp aizawai, kurstaki,Bacillus thuringiensis delta endotoxin, baculovirus, entomopathogenicbacteria, virus and fungi.

Bactericides: chlortetracycline, oxytetracycline, streptomycin.

Other biological agents: enrofloxacin, febantel, penethamate, moloxicam,cefalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin,benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovecin,tulathromycin, ceftiour, carprofen, metaflumizone, praziquarantel,triclabendazole.

When used in combination with other active ingredients, the compounds ofthe invention are preferably used in combination with imidacloprid,enrofloxacin, praziquantel, pyrantel embonate, febantel, penethamate,moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, fipronil,ivermectin, omeprazole, tiamulin, benazepril, milbemycin, cyromazine,thiamethoxam, pyriprole, deltamethrin, cefquinome, florfenicol,buserelin, cefovecin, tulathromycin, ceftiour, selamectin, carprofen,metaflumizone, moxidectin, methoprene (including S-methoprene),clorsulon, pyrantel, amitraz, triclabendazole, avermectin, abamectin,emamectin, eprinomectin, doramectin, selamectin, nemadectin,albendazole, cambendazole, fenbendazole, flubendazole, mebendazole,oxfendazole, oxibendazole, parbendazole, tetramisole, levamisole,pyrantel pamoate, oxantel, morantel, triclabendazole, epsiprantel,fipronil, lufenuron, ecdysone or tebufenozide; more preferably,enrofloxacin, praziquantel, pyrantel embonate, febantel, penethamate,moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, omeprazole,tiamulin, benazepril, pyriprole, cefquinome, florfenicol, buserelin,cefovecin, tulathromycin, ceftiour, selamectin, carprofen, moxidectin,clorsulon, pyrantel, eprinomectin, doramectin, selamectin, nemadectin,albendazole, cambendazole, fenbendazole, flubendazole, mebendazole,oxfendazole, oxibendazole, parbendazole, tetramisole, levamisole,pyrantel pamoate, oxantel, morantel, triclabendazole, epsiprantel,lufenuron or ecdysone; even more preferably, enrofloxacin, praziquantel,pyrantel embonate, febantel, penethamate, moloxicam, cefalexin,kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril,pyriprole, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin,ceftiour, selamectin, carprofen, moxidectin, clorsulon or pyrantel.

Of particular note is a combination where the additional activeingredient has a different site of action from the compound of formulaI. In certain instances, a combination with at least one other parasiticinvertebrate pest control active ingredient having a similar spectrum ofcontrol but a different site of action will be particularly advantageousfor resistance management. Thus, a combination product of the inventionmay comprise a pesticidally effective amount of a compound of formula Iand pesticidally effective amount of at least one additional parasiticinvertebrate pest control active ingredient having a similar spectrum ofcontrol but a different site of action.

One skilled in the art recognizes that because in the environment andunder physiological conditions salts of chemical compounds are inequilibrium with their corresponding non salt forms, salts share thebiological utility of the non salt forms. Thus a wide variety of saltsof compounds of the invention (and active ingredients used incombination with the active ingredients of the invention) may be usefulfor control of invertebrate pests and animal parasites. Salts includeacid-addition salts with inorganic or organic acids such as hydrobromic,hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric,lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric,4-toluenesulfonic or valeric acids. The compounds of the invention alsoinclude N-oxides. Accordingly, the invention comprises combinations ofcompounds of the invention including N-oxides and salts thereof and anadditional active ingredient including N-oxides and salts thereof.

The compositions for use in animal health may also contain formulationauxiliaries and additives, known to those skilled in the art asformulation aids (some of which may be considered to also function assolid diluents, liquid diluents or surfactants). Such formulationauxiliaries and additives may control: pH (buffers), foaming duringprocessing (antifoams such polyorganosiloxanes), sedimentation of activeingredients (suspending agents), viscosity (thixotropic thickeners),in-container microbial growth (antimicrobials), product freezing(antifreezes), color (dyes/pigment dispersions), wash-off (film formersor stickers), evaporation (evaporation retardants), and otherformulation attributes. Film formers include, for example, polyvinylacetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinylacetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers andwaxes. Examples of formulation auxiliaries and additives include thoselisted in McCutcheon's Volume 2: Functional Materials, annualInternational and North American editions published by McCutcheon'sDivision, The Manufacturing Confectioner Publishing Co.; and PCTPublication WO 03/024222.

The compounds of the invention can be applied without other adjuvants,but most often application will be of a formulation comprising one ormore active ingredients with suitable carriers, diluents, andsurfactants and possibly in combination with a food depending on thecontemplated end use. One method of application involves spraying awater dispersion or refined oil solution of the combination products.Compositions with spray oils, spray oil concentrations, spreaderstickers, adjuvants, other solvents, and synergists such as piperonylbutoxide often enhance compound efficacy. Such sprays can be appliedfrom spray containers such as a can, a bottle or other container, eitherby means of a pump or by releasing it from a pressurized container,e.g., a pressurized aerosol spray can. Such spray compositions can takevarious forms, for example, sprays, mists, foams, fumes or fog. Suchspray compositions thus can further comprise propellants, foamingagents, etc. as the case may be. Of note is a spray compositioncomprising a pesticidally effective amount of a compound of theinvention and a carrier. One embodiment of such a spray compositioncomprises a pesticidally effective amount of a compound of the inventionand a propellant. Representative propellants include, but are notlimited to, methane, ethane, propane, butane, isobutane, butene,pentane, isopentane, neopentane, pentene, hydrofluorocarbons,chlorofluorocarbons, dimethyl ether, and mixtures of the foregoing. Ofnote is a spray composition (and a method utilizing such a spraycomposition dispensed from a spray container) used to control at leastone parasitic invertebrate pest selected from the group consisting ofmosquitoes, black flies, stable flies, deer flies, horse flies, wasps,yellow jackets, hornets, ticks, spiders, ants, gnats, and the like,including individually or in combinations.

The controlling of animal parasites includes controlling externalparasites that are parasitic to the surface of the body of the hostanimal (e.g., shoulders, armpits, abdomen, inner part of the thighs) andinternal parasites that are parasitic to the inside of the body of thehost animal (e.g., stomach, intestine, lung, veins, under the skin,lymphatic tissue). External parasitic or disease transmitting pestsinclude, for example, chiggers, ticks, lice, mosquitoes, flies, mitesand fleas. Internal parasites include heartworms, hookworms andhelminths. The compounds of the invention may be particularly suitablefor combating external parasitic pests. The compounds of the inventionmay be suitable for systemic and/or non-systemic control of infestationor infection by parasites on animals.

The compounds of the invention may be suitable for combating parasiticinvertebrate pests that infest animal subjects including those in thewild, livestock and agricultural working animals. Livestock is the termused to refer (singularly or plurally) to a domesticated animalintentionally reared in an agricultural setting to make produce such asfood or fiber, or for its labor, examples of livestock include cattle,sheep, goats, horses, pigs, donkeys, camels, buffalo, rabbits, hens,turkeys, ducks and geese (e.g., raised for meat, milk, butter, eggs,fur, leather, feathers and/or wool). By combating parasites, fatalitiesand performance reduction (in terms of meat, milk, wool, skins, eggs,etc.) are reduced, so that applying the compounds of the inventionallows more economic and simple husbandry of animals.

The compounds of the invention may be suitable for combating parasiticinvertebrate pests that infest companion animals and pets (e.g., dogs,cats, pet birds and aquarium fish), research and experimental animals(e.g., hamsters, guinea pigs, rats and mice), as well as animals raisedfor/in zoos, wild habitats and/or circuses.

In an embodiment of this invention, the animal is preferably avertebrate, and more preferably a mammal, avian or fish. In a particularembodiment, the animal subject is a mammal (including great apes, suchas humans). Other mammalian subjects include primates (e.g., monkeys),bovine (e.g., cattle or dairy cows), porcine (e.g., hogs or pigs), ovine(e.g., goats or sheep), equine (e.g., horses), canine (e.g., dogs),feline (e.g., house cats), camels, deer, donkeys, buffalos, antelopes,rabbits, and rodents (e.g., guinea pigs, squirrels, rats, mice, gerbils,and hamsters). Avians include Anatidae (swans, ducks and geese),Columbidae (e.g., doves and pigeons), Phasianidae (e.g., partridges,grouse and turkeys), Thesienidae (e.g., domestic chickens), Psittacines(e.g., parakeets, macaws, and parrots), game birds, and ratites (e.g.,ostriches).

Birds treated or protected by the compounds of the invention can beassociated with either commercial or noncommercial aviculture. Theseinclude Anatidae, such as swans, geese, and ducks, Columbidae, such asdoves and domestic pigeons, Phasianidae, such as partridge, grouse andturkeys, Thesienidae, such as domestic chickens, and Psittacines, suchas parakeets, macaws and parrots raised for the pet or collector market,among others.

For purposes of the present invention, the term “fish” is understood toinclude without limitation, the Teleosti grouping of fish, i.e.,teleosts. Both the Salmoniformes order (which includes the Salmonidaefamily) and the Perciformes order (which includes the Centrarchidaefamily) are contained within the Teleosti grouping. Examples ofpotential fish recipients include the Salmonidae, Serranidae, Sparidae,Cichlidae, and Centrarchidae, among others.

Other animals are also contemplated to benefit from the inventivemethods, including marsupials (such as kangaroos), reptiles (such asfarmed turtles), and other economically important domestic animals forwhich the inventive methods are safe and effective in treating orpreventing parasite infection or infestation.

Examples of parasitic invertebrate pests controlled by administering apesticidally effective amount of the compounds of the invention to ananimal to be protected include ectoparasites (arthropods, acarines,etc.) and endoparasites (helminths, e.g., nematodes, trematodes,cestodes, acanthocephalans, etc.).

The disease or group of diseases described generally as helminthiasis isdue to infection of an animal host with parasitic worms known ashelminths. The term ‘helminths’ is meant to include nematodes,trematodes, cestodes and acanthocephalans. Helminthiasis is a prevalentand serious economic problem with domesticated animals such as swine,sheep, horses, cattle, goats, dogs, cats and poultry.

Among the helminths, the group of worms described as nematodes causeswidespread and at times serious infection in various species of animals.

Nematodes that are contemplated to be treated by the compounds of theinvention include, without limitation, the following genera:Acanthocheilonema, Aelurostrongylus, Ancylostoma, Angiostrongylus,Ascaridia, Ascaris, Brugia, Bunostomum, Capillaria, Chabertia, Cooperia,Crenosoma, Dictyocaulus, Dioctophyme, Dipetalonema, Diphyllobothrium,Dirofilaria, Dracunculus, Enterobius, Filaroides, Haemonchus, Heterakis,Lagochilascaris, Loa, Mansonella, Muellerius, Necator, Nematodirus,Oesophagostomum, Ostertagia, Oxyuris, Parafilaria, Parascaris,Physaloptera, Protostrongylus, Setaria, Spirocerca, Stephanofilaria,Strongyloides, Strongylus, Thelazia, Toxascaris, Toxocara, Trichinella,Trichonema, Trichostrongylus, Trichuris, Uncinaria and Wuchereria.

Of the above, the most common genera of nematodes infecting the animalsreferred to above are Haemonchus, Trichostrongylus, Ostertagia,Nematodirus, Cooperia, Ascaris, Bunostomum, Oesophagostomum, Chabertia,Trichuris, Strongylus, Trichonema, Dictyocaulus, Capillaria, Heterakis,Toxocara, Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxascaris andParascaris. Certain of these, such as Nematodirus, Cooperia andOesophagostomum attack primarily the intestinal tract while others, suchas Haemonchus and Ostertagia, are more prevalent in the stomach whileothers such as Dictyocaulus are found in the lungs. Still otherparasites may be located in other tissues such as the heart and bloodvessels, subcutaneous and lymphatic tissue and the like.

Trematodes that are contemplated to be treated by the invention and bythe inventive methods include, without limitation, the following genera:Alaria, Fasciola, Nanophyetus, Opisthorchis, Paragonimus andSchistosoma.

Cestodes that are contemplated to be treated by the invention and by theinventive methods include, without limitation, the following genera:Diphyllobothrium, Diplydium, Spirometra and Taenia.

The most common genera of parasites of the gastrointestinal tract ofhumans are Ancylostoma, Necator, Ascaris, Strongy hides, Trichinella,Capillaria, Trichuris and Enterobius. Other medically important generaof parasites which are found in the blood or other tissues and organsoutside the gastrointestinal tract are the filarial worms such asWuchereria, Brugia, Onchocerca and Loa, as well as Dracunculus and extraintestinal stages of the intestinal worms Strongyloides and Trichinella.

Numerous other helminth genera and species are known to the art, and arealso contemplated to be treated by the compounds of the invention. Theseare enumerated in great detail in Textbook of Veterinary ClinicalParasitology, Volume 1, Helminths, E. J. L. Soulsby, F. A. Davis Co.,Philadelphia, Pa.; Helminths, Arthropods and Protozoa, (6^(th) tEditionof Monnig's Veterinary Helminthology and Entomology), E. J. L. Soulsby,Williams and Wilkins Co., Baltimore, Md.

The compounds of the invention may be effective against a number ofanimal ectoparasites (e.g., arthropod ectoparasites of mammals andbirds).

Insect and acarine pests include, e.g., biting insects such as flies andmosquitoes, mites, ticks, lice, fleas, true bugs, parasitic maggots, andthe like.

Adult flies include, e.g., the horn fly or Haematobia irritans, thehorse fly or Tabanus spp., the stable fly or Stomoxys calcitrans, theblack fly or Simulium spp., the deer fly or Chrysops spp., the louse flyor Melophagus ovinus, and the tsetse fly or Glossina spp.

Parasitic fly maggots include, e.g., the bot fly (Oestrus ovis andCuterebra spp.), the blow fly or Phaenicia spp., the screwworm orCochliomyia hominivorax, the cattle grub or Hypoderma spp., thefleeceworm and the Gastrophilus of horses. Mosquitoes include, forexample, Culex spp., Anopheles spp. and Aedes spp.

Mites include Mesostigmalphatalpha spp. e.g., mesostigmatids such as thechicken mite, Dermalphanyssus galphallinalphae; itch or scab mites suchas Sarcoptidae spp. for example, Salpharcoptes scalphabiei; mange mitessuch as Psoroptidae spp. including Chorioptes bovis and Psoroptes ovis;chiggers e.g., Trombiculidae spp. for example the North Americanchigger, Trombiculalpha alphalfreddugesi.

Ticks include, e.g., soft-bodied ticks including Argasidae spp. forexample Argalphas spp. and Ornithodoros spp.; hard-bodied ticksincluding Ixodidae spp., for example Rhipicephalphalus sanguineus,Dermacentor variabilis, Dermacentor andersoni, Amblyomma americanum,Ixodes scapularis and other Rhipicephalus spp. (including the formerBoophilus genera).

Lice include, e.g., sucking lice, e.g., Menopon spp. and Bovicola spp.;biting lice, e.g., Haematopinus spp., Linognathus spp. and Solenopotesspp.

Fleas include, e.g., Ctenocephalides spp., such as dog flea(Ctenocephalides canis) and cat flea (Ctenocephalides felis); Xenopsyllaspp. such as oriental rat flea (Xenopsylla cheopis); and Pulex spp. suchas human flea (Pulex irritans).

True bugs include, e.g., Cimicidae or e.g., the common bed bug (Cimexlectularius); Triatominae spp. including triatomid bugs also known askissing bugs; for example Rhodnius prolixus and Triatoma spp.

Generally, flies, fleas, lice, mosquitoes, gnats, mites, ticks andhelminths cause tremendous losses to the livestock and companion animalsectors. Arthropod parasites also are a nuisance to humans and canvector disease-causing organisms in humans and animals.

Numerous other parasitic invertebrate pests are known to the art, andare also contemplated to be treated by the compounds of the invention.These are enumerated in great detail in Medical and VeterinaryEntomology, D. S. Kettle, John Wiley AND Sons, New York and Toronto;Control of Arthropod Pests of Livestock: A Review of Technology, R. O.Drummand, J. E. George, and S. E. Kunz, CRC Press, Boca Raton, FIa.

The compounds of the invention may also be effective againstectoparasites including: flies such as Haematobia (Lyperosia) irritans(horn fly), Simulium spp. (blackfly), Glossina spp. (tsetse flies),Hydrotaea irritans (head fly), Musca autumnalis (face fly), Muscadomestica (house fly), Morellia simplex (sweat fly), Tabanus spp. (horsefly), Hypoderma bovis, Hypoderma lineatum, Lucilia sericata, Luciliacuprina (green blowfly), Calliphora spp. (blowfly), Protophormia spp.,Oestrus ovis (nasal botfly), Culicoides spp. (midges), Hippoboscaequine, Gastrophilus intestinalis, Gastrophilus haemorrhoidalis andGastrophilus nasalis; lice such as Bovicola (Damalinia) bovis, Bovicolaequi, Haematopinus asini, Felicola subrostratus, Heterodoxus spiniger,Lignonathus setosus and Trichodectes canis; keds such as Melophagusovinus; and mites such as Psoroptes spp., Sarcoptes scabei, Chorioptesbovis, Demodex equi, Cheyletiella spp., Notoedres cati, Trombicula spp.and Otodectes cyanotis (ear mites).

Treatments of the invention are by conventional means such as by enteraladministration in the form of, for example, tablets, capsules, drinks,drenching preparations, granulates, pastes, boli, feed-throughprocedures, or suppositories; or by parenteral administration, such as,for example, by injection (including intramuscular, subcutaneous,intravenous, intraperitoneal) or implants; or by nasal administration.

When compounds of the invention are applied in combination with anadditional biologically active ingredient, they may be administeredseparately e.g. as separate compositions. In this case, the biologicallyactive ingredients may be administered simultaneously or sequentially.Alternatively, the biologically active ingredients may be components ofone composition.

The compounds of the invention may be administered in a controlledrelease form, for example in subcutaneous or orally adminstered slowrelease formulations.

Typically a parasiticidal composition according to the present inventioncomprises a compound of the invention, optionally in combination with anadditional biologically active ingredient, or N-oxides or salts thereof,with one or more pharmaceutically or veterinarily acceptable carrierscomprising excipients and auxiliaries selected with regard to theintended route of administration (e.g., oral or parenteraladministration such as injection) and in accordance with standardpractice. In addition, a suitable carrier is selected on the basis ofcompatibility with the one or more active ingredients in thecomposition, including such considerations as stability relative to pHand moisture content. Therefore of note are compounds of the inventionfor protecting an animal from an invertebrate parasitic pest comprisinga parasitically effective amount of a compound of the invention,optionally in combination with an additional biologically activeingredient and at least one carrier.

For parenteral administration including intravenous, intramuscular andsubcutaneous injection, the compounds of the invention can be formulatedin suspension, solution or emulsion in oily or aqueous vehicles, and maycontain adjuncts such as suspending, stabilizing and/or dispersingagents.

The compounds of the invention may also be formulated for bolusinjection or continuous infusion. Pharmaceutical compositions forinjection include aqueous solutions of water-soluble forms of activeingredients (e.g., a salt of an active compound), preferably inphysiologically compatible buffers containing other excipients orauxiliaries as are known in the art of pharmaceutical formulation.Additionally, suspensions of the active compounds may be prepared in alipophilic vehicle. Suitable lipophilic vehicles include fatty oils suchas sesame oil, synthetic fatty acid esters such as ethyl oleate andtriglycerides, or materials such as liposomes.

Aqueous injection suspensions may contain substances that increase theviscosity of the suspension, such as sodium carboxymethyl cellulose,sorbitol, or dextran. Formulations for injection may be presented inunit dosage form, e.g., in ampoules or in multi-dose containers.Alternatively, the active ingredient may be in powder form forconstitution with a suitable vehicle, e.g., sterile, pyrogen-free water,before use.

In addition to the formulations described supra, the compounds of theinvention may also be formulated as a depot preparation. Such longacting formulations may be administered by implantation (for example,subcutaneously or intramuscularly) or by intramuscular or subcutaneousinjection.

The compounds of the invention may be formulated for this route ofadministration with suitable polymeric or hydrophobic materials (forinstance, in an emulsion with a pharmacologically acceptable oil), withion exchange resins, or as a sparingly soluble derivative such as,without limitation, a sparingly soluble salt.

For administration by inhalation, the compounds of the invention can bedelivered in the form of an aerosol spray using a pressurized pack or anebulizer and a suitable propellant, e.g., without limitation,dichlorodifluoromethane, trichlorofluoromethane,dichlorotetrafluoroethane or carbon dioxide. In the case of apressurized aerosol, the dosage unit may be controlled by providing avalve to deliver a metered amount. Capsules and cartridges of, forexample, gelatin for use in an inhaler or insufflator may be formulatedcontaining a powder mix of the compound and a suitable powder base suchas lactose or starch.

The compounds of the invention may have favourable pharmacokinetic andpharmacodynamic properties providing systemic availability from oraladministration and ingestion. Therefore after ingestion by the animal tobe protected, parasiticidally effective concentrations of a compound ofthe invention in the bloodstream may protect the treated animal fromblood-sucking pests such as fleas, ticks and lice. Therefore of note isa composition for protecting an animal from an invertebrate parasitepest in a form for oral administration (i.e. comprising, in addition toa parasiticidally effective amount of a compound of the invention, oneor more carriers selected from binders and fillers suitable for oraladministration and feed concentrate carriers).

For oral administration in the form of solutions (the most readilyavailable form for absorption), emulsions, suspensions, pastes, gels,capsules, tablets, boluses, powders, granules, rumen-retention andfeed/water/lick blocks, the compounds of the invention can be formulatedwith binders/fillers known in the art to be suitable for oraladministration compositions, such as sugars and sugar derivatives (e.g.,lactose, sucrose, mannitol, sorbitol), starch (e.g., maize starch, wheatstarch, rice starch, potato starch), cellulose and derivatives (e.g.,methylcellulose, carboxymethylcellulose, ethylhydroxycellulose), proteinderivatives (e.g., zein, gelatin), and synthetic polymers (e.g.,polyvinyl alcohol, polyvinylpyrrolidone). If desired, lubricants (e.g.,magnesium stearate), disintegrating agents (e.g., cross-linkedpolyvinylpyrrolidinone, agar, alginic acid) and dyes or pigments can beadded. Pastes and gels often also contain adhesives (e.g., acacia,alginic acid, bentonite, cellulose, xanthan gum, colloidal magnesiumaluminum silicate) to aid in keeping the composition in contact with theoral cavity and not being easily ejected.

In one embodiment a composition of the present invention is formulatedinto a chewable and/or edible product (e.g., a chewable treat or edibletablet). Such a product would ideally have a taste, texture and/or aromafavored by the animal to be protected so as to facilitate oraladministration of the compounds of the invention.

If the parasiticidal compositions are in the form of feed concentrates,the carrier is typically selected from high-performance feed, feedcereals or protein concentrates. Such feed concentrate-containingcompositions can, in addition to the parasiticidal active ingredients,comprise additives promoting animal health or growth, improving qualityof meat from animals for slaughter or otherwise useful to animalhusbandry. These additives can include, for example, vitamins,antibiotics, chemotherapeutics, bacteriostats, fungistats, coccidiostatsand hormones.

The compound of the invention may also be formulated in rectalcompositions such as suppositories or retention enemas, using, e.g.,conventional suppository bases such as cocoa butter or other glycerides.

The formulations for the method of this invention may include anantioxidant, such asBHT (butylated hydroxytoluene). The antioxidant isgenerally present in amounts of at 0.1-5 percent (wt/vol). Some of theformulations require a solubilizer, such as oleic acid, to dissolve theactive agent, particularly if spinosad is included. Common spreadingagents used in these pour-on formulations include isopropyl myristate,isopropyl palmitate, caprylic/capric acid esters of saturated C₁₂-C₁₈fatty alcohols, oleic acid, oleyl ester, ethyl oleate, triglycerides,silicone oils and dipropylene glycol methyl ether. The pour-onformulations for the method of this invention are prepared according toknown techniques. Where the pour-on is a solution, theparasiticide/insecticide is mixed with the carrier or vehicle, usingheat and stirring if required. Auxiliary or additional ingredients canbe added to the mixture of active agent and carrier, or they can bemixed with the active agent prior to the addition of the carrier.Pour-on formulations in the form of emulsions or suspensions aresimilarly prepared using known techniques.

Other delivery systems for relatively hydrophobic pharmaceuticalcompounds may be employed. Liposomes and emulsions are well-knownexamples of delivery vehicles or carriers for hydrophobic drugs. Inaddition, organic solvents such as dimethylsulfoxide may be used, ifneeded.

The rate of application required for effective parasitic invertebratepest control (e.g. “pesticidally effective amount”) will depend on suchfactors as the species of parasitic invertebrate pest to be controlled,the pest's life cycle, life stage, its size, location, time of year,host crop or animal, feeding behavior, mating behavior, ambientmoisture, temperature, and the like. One skilled in the art can easilydetermine the pesticidally effective amount necessary for the desiredlevel of parasitic invertebrate pest control.

In general for veterinary use, the compounds of the invention areadministered in a pesticidally effective amount to an animal,particularly a homeothermic animal, to be protected from parasiticinvertebrate pests.

A pesticidally effective amount is the amount of active ingredientneeded to achieve an observable effect diminishing the occurrence oractivity of the target parasitic invertebrate pest. One skilled in theart will appreciate that the pesticidally effective dose can vary forthe various compounds and compositions useful for the method of thepresent invention, the desired pesticidal effect and duration, thetarget parasitic invertebrate pest species, the animal to be protected,the mode of application and the like, and the amount needed to achieve aparticular result can be determined through simple experimentation.

For oral or parenteral administration to animals, a dose of thecompositions of the present invention administered at suitable intervalstypically ranges from about 0.01 mg/kg to about 100 mg/kg, andpreferably from about 0.01 mg/kg to about 30 mg/kg of animal bodyweight.

Suitable intervals for the administration of the compositions of thepresent invention to animals range from about daily to about yearly. Ofnote are administration intervals ranging from about weekly to aboutonce every 6 months. Of particular note are monthly administrationintervals (i.e. administering the compounds to the animal once everymonth).

The following Examples illustrate, but do not limit, the invention.

PREPARATION EXAMPLES Example I11-(4-Bromo-3-methyl-phenyl)-2-(triphenylphosphanylidene)-ethanone (Va)

1300 mg of 2-Bromo-1-(4-bromo-3-methyl-phenyl)-ethanone (VIIa) (Journalof Organic Chemistry (1947), 12, 617-703) was stirred with 1300 mg oftriphenylphosphine in 20 ml of dichloromethane at ambient temperaturefor 18 hours. The mixture was diluted with toluene and the separatedphosphonium salt was filtered off. It was then suspended in 20 ml ofdichloromethane and 20 ml of water. 800 mg (7.55 mmol) of sodiumbicarbonate was then added in 20 ml of water and the mixture was stirredovernight. The organic layer was separated, dried and evaporated underreduced pressure. The residue was triturated with hexane giving 1.6 g(86%) of1-(4-Bromo-3-methyl-phenyl)-2-(triphenylphosphanylidene)-ethanone (Va)as a solid. ¹H-NMR (CDCl₃, δ in ppm): 7.40-7.90 (m, 18H), 4.40 (m, 1H).

Example I21-(4-Bromo-3-methyl-phenyl)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-but-2-en-1-one(IVa)

473 mg of1-(4-Bromo-3-methyl-phenyl)-2-(triphenylphosphanylidene)-ethanone (Va)was refluxed with 243 mg of1-(3,5-Dichloro-phenyl)-2,2,2-trifluoro-ethanone (VIa) (Journal ofPhysical Organic Chemistry (1989), 2(4), 363-6) in 3 ml of toluene for 3hours. The solvent was then evaporated, and the residue was trituratedwith the mixture hexane:ethyl acetate 20:1. The solid that separated wasfiltered off and the filtrate after evaporation was purified on silicagel (40 g, hexane:acetate 10:1) giving 380 mg (86%) of1-(4-Bromo-3-methyl-phenyl)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-but-2-en-1-one(IVa) as a yellow oil which solidified on standing (mixture of E and Zisomers). ¹H-NMR (CDCl₃, δ in ppm): 2.41 (s) and 2.46 (s) (total of 3H),6.80-7.80 (m, total of 7H).

Example I33-(4-Bromo-3-methyl-phenyl)-5-(3,5-dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazole(IIIa)

300 mg1-(4-Bromo-3-methyl-phenyl)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-but-2-en-1-one(IVa), 80 mg MeNHOH.HCl and 100 mg triethylamine were refluxed in 2 mlof ethanol for 18 hours. After evaporation of the solvent the residuewas purified on silica gel giving 210 mg (65%) of3-(4-Bromo-3-methyl-phenyl)-5-(3,5-dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazole(IIIa) as a colorless resin.

7.56 (d, 1H), 7.44 (s, 2H), 7.36 (t, 1H), 7.33 (d, 1H), 7.13 (dd, 1H),5.35 (s, 1H), 2.95 (s, 3H), 2.40 (s, 3H).

Example I44-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid (IIa)

210 mg of3-(4-Bromo-3-methyl-phenyl)-5-(3,5-dichlom-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazole(IIIa) was dissolved in 20 ml of dry THF, cooled to −90° C. and treatedwith 0.625 ml BuLi 1.6M in hexane. The mixture was stirred for 1 hour at−80° C. and then a great excess of solid CO₂ was added to the mixture.The temperature was allowed to rise up to −30° C. (1 hour) and 5 ml of1M HCl was added followed with ether. The organic layer was dried andevaporated to dryness. The residual resin was used in the final stepwithout purification.

Example P1 (Compound A3 from Table A):N-Butyl-4-[5-(3,5-dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzamide

200 mg of4-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid (IIa), 127 mg of oxalylchloride and one drop of DMF were stirred in10 ml of dichloromethane overnight. The volatiles were evaporated underreduced pressure, the residue was dissolved in 5 ml of dichloromethaneand then treated with 150 mg of n-butylamine. The mixture was stirred atambient temperature for 3 hours, washed with diluted HCl and afterevaporation the residue was purified on silica gel giving 65 mg ofN-Butyl-4-[5-(3,5-dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzamide(Ia) as a colorless resin. ¹H-NMR (CDCl₃, δ in ppm): 7.23-7.51 (m, 6H),5.70 (t, 1H), 5.31 (s, 1H), 3.49 (q, 2H), 2.98 (s, 3H), 2.37 (s, 3H),1.61 (m, 2H), 1.45 (m, 2H), 0.96 (t, 3H).

Example I54-[3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoicacid ethyl ester (XVIIa)

To a solution of 1 g1-(4-Bromo-3-methyl-phenyl)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-but-2-en-1-one(IVa) in 40 ml of absolute ethanol was added 1 ml of triethylamine and150 mg of PdCl₂(PPh₃)₂. The mixture was then heated in an autoclaveunder 60 bar of CO at 120° C. for 20 hours. Concentration of the mixturefollowed by column chromatography (silica gel) afforded 0.66 g (67%) of4-[3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoicacid ethyl ester (IXa) as an oil, which crystallized on standing. ¹H-NMR(CDCl₃, 8 in ppm): 7.93 (q, 1H), 7.66 (m, 2H), 7.15-7.39 (m, 4H), 4.38(q, 2H), 2.62 (s, 3H), 1.40 (t, 3H).

Example I64-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid ethyl ester (VIIIa)

0.62 g of4-[3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoicacid ethyl ester (XVIIa) was mixed with 0.21 g of N-methylhydroxylaminehydrochloride and 0.42 ml of triethylamine in 10 ml of dry ethanol. Themixture was refluxed for 20 hours, evaporated to dryness and purified onsilica gel giving 0.275 g (42%) of4-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid ethyl ester (VIIIa) as a colorless oil. ¹H-NMR (CDCl₃, δ in ppm):7.93 (d, 1H), 7.30-7.45 (m, 5H), 5.43 (s, 1H), 4.37 (q, 2H), 2.99 (s,3H), 2.61 (s, 3H), 1.40 (t, 3H).

Example I74-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid (IIa)

0.27 g of4-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid ethyl ester (VIIIa) was stirred in a mixture of 5 ml of methanol, 5ml of THF and 1 ml of water. To this solution 0.2 g KOH was added andthe mixture was stirred for 5 days at ambient temperature. The solventswere then evaporated, the residue was diluted with water and acidifiedwith 1N HCl. The solid that precipitated was isolated by filtration anddried to give 0.240 g (95%,) of4-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid (IIa) as a pale solid. ¹H-NMR (CDCl₃, δ in ppm): 8.05 (d, 1H),7.26-7.44 (m, 5H), 5.46 (s, 1H), 3.00 (s, 3H), 2.65 (s, 3H).

Example I8 Preparation of4-[5-(3,5-Dichloro-phenyl)-2,5-dimethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzamide

To a solution of4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzamide(200 mg) in 1,2-dichloroethane (3 ml) was added trimethyloxoniumtetrafluoroborate (85 mg) and the reaction mixture was stirred at roomtemperature for 19 hours then more trimethyloxonium tetrafluoroborate(210 mg). After 4 hours 30 minutes, more trimethyloxoniumtetrafluoroborate (0.5 ml) was added and after 2 hours, the reactionmixture was heated at (85° C.) for 18 hours. The solution was thenconcentrated under vacuo to give a crude residue (210 mg). Part of thisresidue (100 mg) of the crude was extracted between AcOEt and saturatedNaHCO₃. The organic phases were gathered, dried over anhydrous MgSO₄,filtered and evaporated to give the desired compound (54 mg). ¹H-NMR(CDCl₃, δ in ppm): 7.50-7.31 (m, 6H), 5.75 (bs, 2H), 5.41 (s, 1H), 2.99(s, 3H), 2.52 (s, 3H).

The preparation of4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzamideis disclosed in WO 2005/085216.

Example I9 Preparation of3-(4-tert-Butoxycarbonyl-3-methyl-phenyl)-5-(3,5-dichloro-phenyl)-5-methyl-5H-isoxazole-2-carboxylicacid methyl ester

To a solution of4-[5-(3,5-Dichloro-phenyl)-5-methyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid tert-butyl ester (1.3 g) in dry tetrahydrofuran (15 ml) stirredunder argon at −78° C., was added lithium hexamethyldisilazane (“LHMDS”)(1 M in hexane) (3.45 ml). The solution was stirred at −78° C. untildeprotonation was completed as monitored by thin layer chromatography.Then, to this solution was added methyl chloroformate (0.465 ml) and thereaction mixture was stirred at −78° C. for 2 hours. The mixture wasquenched with saturated ammonium chloride and then extracted with ethylacetate. The combined organic extracts were dried over magnesium sulfateand concentrated. The residue was purified by chromatography on silicagel (eluent: heptane/diisopropylether 1:1) to give3-(4-tert-butoxycarbonyl-3-methyl-phenyl)-5-(3,5-dichloro-phenyl)-5-methyl-5H-isoxazole-2-carboxylicacid methyl ester (472 mg) as a yellow foam.

¹H-NMR (CDCl₃, 400 MHz): 7.84 (d, 1H, J=8.44 Hz), 7.50 (m, 2H), 7.43 (m,1H), 7.35 (m, 2H), 5.70 (s, 1H), 3.81 (s, 3H), 2.59 (s, 3H), 1.60 (s,9H) ppm.

Similarly,3-(4-tert-Butoxycarbonyl-3-methyl-phenyl)-5-(3,5-dichloro-phenyl)-5-methyl-5H-isoxazole-2-carboxylicacid ethyl ester was obtained using ethylchloroformate as anelectrophile. ¹H-NMR (CDCl₃, 400 MHz): 7.84 (d, 1H, J=8.80 Hz), 7.51 (m,2H), 7.43 (m, 1H), 7.37 (m, 2H), 5.71 (s, 1H), 4.24 (q, 2H, J=6.97 Hz),2.59 (s, 3H), 1.60 (s, 9H), 1.28 (t, 3H, J=6.97 Hz), ppm.

4-[5-(3,5-Dichloro-phenyl)-5-methyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid tert-butyl ester is disclosed in WO 2009/080250

Example I105-[3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-fluoro-benzonitrile

163 mg of 1-(3,5-Dichloro-phenyl)-2,2,2-trifluor-ethanone (VIa) (Journalof Physical Organic Chemistry (1989), 2(4), 363-6), 486 mg of5-acetyl-2-fluoro-benzonitrile (CAS:288309-07-9) and 276 mg of potassiumcarbonate in 5 ml of dry toluene were refluxed for 72 hours. The solventwas then evaporated under reduced pressure and the residue was purifiedon silica gel (eluent hexane/ethyl acetate 6:1) affording5-[3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-fluoro-benzonitrileas a yellow resin in 46% yield (solidified on standing). ¹H-NMR (CDCl₃,δ in ppm): 8.05-8.11 (m, 2H), 7.33-7.43 (m, 3H), 7.15 (s, 2H).

Example I115-[3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-[1,2,4]triazol-1-yl-benzonitrile

310 mg of5-[3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-fluoro-benzonitrile(Example I10) 73 mg of 1,2,4-triazole and 166 mg of potassium carbonatewere stirred in 5 ml acetonitrile at room temperature for 24 hours. Thesolid was filtered off and the filtrate was evaporated under reducedpressure. The residue was purified on silica gel (elutant diethylether)affording5-[3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-[1,2,4]triazol-1-yl-benzonitrileas a solid in 71% yield. ¹H-NMR (CDCl₃, δ in ppm): 8.96 (s, 1H),8.17-8.28 (m, 3H), 7.99 (d, 1H), 7.37-7.39 (m, 2H), 7.17 (s, 2H).

Example P25-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydm-isoxazol-3-yl]-2-[1,2,4]triazol-1-yl-benzonitrile(Compound No. C1)

437 mg of5-[3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-[1,2,4]triazol-1-yl-benzonitrile(Example I11), 85 mg of N-methylhydroxylamine hydrochloride and 103 mgtriethylamine were dissolved in 25 ml ethanol and refluxed for 72 hours.Evaporation of the solvent and purification on silica gel (eluenthexane/ethyl acetate 1:1) afforded 200 mg of a mixture of the productand the starting enone. The mixture was treated with an excess ofmethylhydroxylamine hydrochloride (200 mg) and TEA (300 mg) in refluxingethanol for 30 min. Evaporation of the solvent and purification onsilica gel (hexane/ethyl acetate 2:1) afforded5-[5-(3,5-dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-[1,2,4]triazol-1-yl-benzonitrile(27 mg) as a resin. ¹H-NMR (CDCl₃, δ in ppm): 8.86 (s, 1H), 8.21 (s,1H), 7.83-7.95 (m, 3H), 7.39-7.45 (m, 3H), 5.55 (s, 1H), 3.02 (s, 3H).

Example I12{4-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-phenyl}-methanol

414 mg of4-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid ethyl ester (VIIIa) and 152 mg of sodium borohydride were suspendedin 10 ml tetrahydrofurane. The mixture was heated to 60° C. and 0.85 mlof methanol was the added dropwise under vigorous stirring. The mixturewas stirred at 60° C. until the gas evolution subsided. The mixture wasthen cooled and ice water followed by diethylether were added. Then asolution of hydrochloric acid (1N) was slowly added to acidify thesolution. The organic phase was washed with water and dried. Evaporationof the solvent afforded{4-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-phenyl}-methanolas a solidified foam in 98% yield. ¹H-NMR (CDCl₃, δ in ppm): 7.28-7.45(m, 6H), 5.34 (s, 1H), 4.72 (s, 2H), 2.99 (s, 3H), 2.35 (s, 3H).

Example I133-(4-Chloromethyl-3-methyl-phenyl)-5-(3,5-dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazole

690 mg of{4-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-phenyl}-methanolwas dissolved in 20 ml dichloromethane and one drop ofN,N-dimethylformamide was then added. Thionylchloride (216 mg) was thenadded very slowly at room temperature. The mixture turned slight yellowbefore the end of the addition. The mixture was stirred for 3 hours atambient temperature and then evaporated to dryness. The residue wasdissolved in diethylether, washed with aqueous sodium bicarbonate, thenwith water and finally dried over anhydrous sodium sulfate. The organicphase was then evaporated to dryness affording3-(4-chloromethyl-3-methyl-phenyl)-5-(3,5-dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazoleas a resinous product (99% yield), which was used immediately for thefurther step without purification. ¹H-NMR (CDCl₃, δ in ppm): 7.29-7.44(m, 6H), 5.36 (s, 1H), 4.60 (s, 2H), 2.99 (s, 3H), 2.44 (s, 3H).

Example I142-{4-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzyl}-isoindole-1,3-dione

524 mg of3-(4-Chloromethyl-3-methyl-phenyl)-5-(3,5-dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazole,216 mg of potassium phthalimide and 10 mg sodium iodide in 7 mlN,N-dimethylformamide were stirred at ambient temperature overnight. Themixture was diluted with water (100 ml) and extracted with 200 ml ofether. The organic phase was washed with water and dried. Evaporation ofthe solvent afforded a foam. Trituration with hexane gave2-{4-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzyl}-isoindole-1,3-dioneas a white solid in 98% yield. ¹H-NMR (CDCl₃, δ in ppm): 7.88 (m, 2H),7.75 (m, 2H), 7.22-7.43 (m, 6H), 5.30 (s, 1H), 4.86 (s, 2H), 2.96 (s,3H), 2.50 (s, 3H).

Example I154-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzylamine

837 mg of2-{4-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzyl}-isoindole-1,3-dione(Example I14) and 500 mg hydrazine hydrate in 25 ml ethanol were heatedat reflux for 2 hours under stirring. The mixture was cooled and dilutedwith diethyl ether. The solid was filtered off and the filtrate wasevaporated. The residue was dissolved in 100 ml of ether and washed withwater. The organic phase was dried and evaporated. The residue waspurified on silica gel (eluent dichloromethane/methanol 4:1) affording4-[5-(3,5-dichloro-phenyl)-2-methyl-5-trifluormethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzylamineas a resin in 65% yield. ¹H-NMR (CDCl₃, δ in ppm): 7.44 (s, 2H), 7.37(m, 2H), 7.28 (m, 2H), 5.33 (s, 1H), 3.88 (s, 2H), 2.99 (s, 3H), 2.34(s, 3H).

The compounds of Table A were prepared in a similar manner as describedin Example P1.

The compounds of Table B were prepared from4-[5-(3,5-Dichloro-phenyl)-2-methyl-5-trifluoromethyl-2,5-dihydro-isoxazol-3-yl]-2-methyl-benzylamine(Example I15) by methods known per se.

The following abbreviations were used throughout this section:s=singlet; bs=broad singlet; d=doublet; dd=double doublet; dt=doubletriplet; t=triplet, tt=triple triplet, q=quartet, sept=septet;m=multiplet; Me=methyl; Et=ethyl; Pr=propyl; Bu=butyl; RT=retentiontime; MH⁺=molecular cation.

The following LC-MS method was used to characterize the compounds:

Method A:

MS ZQ Mass Spectrometer from Waters (single quadrupole massspectrometer), ionization method: electrospray, polarity: positiveionization, capillary (kV) 3.00, cone (V) 30.00, extractor (V) 3.00,source temperature (° C.) 100, desolvation temperature (° C.) 200, conegas flow (L/Hr) 200, desolvation gas flow (L/Hr) 250, mass range: 150 to800 Da. LC 1100er Series HPLC from Agilent: quaternary pump, heatedcolumn compartment and diode-array detector. Column: Waters Atlantisdc18; length: 20 mm; internal diameter: 3 mm; particle size: 3 μm,temperature (° C.) 40, DAD wavelength range (nm): 200 to 500, solventgradient: A = 0.1% of formic acid in water and B: 0.1% of formic acid inacetonitrile. Time (min) A % B % Flow (ml/min) 0.0 90  10 1.7 5.5  0.0100 1.7 5.8  0.0 100 1.7 5.9 90  10 1.7Method B:ACQUITY SQD Mass Spectrometer from Waters (Single quadrupole massspectrometer)Ionisation method: ElectrosprayPolarity: positive ionsCapillary (kV) 3.00, Cone (V) 20.00, Extractor (V) 3.00, SourceTemperature (° C.) 150, Desolvation Temperature (° C.) 400, Cone GasFlow (IUHr) 60, Desolvation Gas Flow (L/Hr) 700Mass range: 100 to 800 DaDAD Wavelength range (nm): 210 to 400Method Waters ACQUITY UPLC with the following HPLC gradient conditions(Solvent A: Water/Methanol 9:1, 0.1% formic acid and Solvent B:Acetonitrile, 0.1% formic acid)

Time (minutes) A (%) B (%) Flow rate (ml/min) 0 100 0 0.75 2.5 0 1000.75 2.8 0 100 0.75 3.0 100 0 0.75Type of column: Waters ACQUITY UPLC HSS T3; Column length: 30 mm;Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron;Temperature: 60° C.

TABLE A Comp No. R¹ R² R⁶ RT (min) MH⁺ Method A1 2,2,2- H Me 4.58513/515/517 A Trifluoro-ethyl A2 Ethyl H Me 4.75 459/461/463 A A3n-Butyl H Me 4.7 487/489/491 A A4 2-Methoxy-1- H Me 4.63 503/505/507 Amethyl-ethyl A5 (1H- H Me 3.22 561/563/565 A Benzo- imidazol-2-yl)-methyl A6 3,3,3- H Me 4.86 527/529/531 A Trifluoro- propyl A7sec-Butyl H Me 5.18 487/489/491 A A8 (Tetrahydro- H Me 4.47 515/517/519A furan-2-yl)- methyl A9 Benzyl H Me 4.44 521/523/525 A A10 2-Fluoro- HMe 4.24 539/541/543 A benzyl A11 1-Phenyl-ethyl H Me 4.78 535/537/539 AA12 4-Methoxy- H Me 4.93 551/553/555 A benzyl A13 1,1-Dioxo- H Me 4.91535/537/539 A thietan-3-yl A14 (6-Chloro- H Me 5.03 556/558/560/ Apyridin-3-yl)- 562 methyl A15 3-Fluoro- H Me 5.07 525/527/529 A phenylA16 Pyridin-2-yl- H Me 4.6 522/524/526 A methyl A17 2,5-Dimethyl- H Me4.89 525/527/529 A 2H-pyrazol-3- yl A18 4-Methyl- H Me 5.19 528/530/532A thiazol-2-yl A19 3-Methyl- H Me 4.89 517/519/521 A thietan-3-yl A201,1-Dimethyl- H Me 5.25 533/535/537 A 2-methyl- sulfanyl- ethyl A211-Oxo-thietan- H Me 4.49 519/521/523 A 3-yl A22 Thietan-3-yl H Me 4.88503/505/507 A A23 Bicyclo[2.2.1] H Me 4.99 525/527/529 A hept-2-yl A24Cyclobutyl H Me 5.02 485/487/489 A A25 H H Me 2.05 429/431/433 A A26Thietan-3-yl H Allyl 2.25 527/529/531 A A27 (R)-2-ethyl- H Me 1.96544/546/548 B isoxazolidin-3- one-4-yl A28 (R)-2-(2,2,2- H Me 2.05598/600/602 B trifluoro- ethyl)- isoxazolidin-3- one-4-yl A29 2-Oxo- HMe 1.89 535/537/539 B [1,2]oxa- thiolan-4-yl A30 2-Oxo- H Me 1.94535/537/539 B [1,2]oxa- thiolan-4-yl A31 2,2,2- H benzyl 2.25589/591/593 B Trifluoro- ethyl A32 Ethyl H benzyl 2.17 535/537/539 B A33Butyl H benzyl 2.32 563/565/567 B A34 2-Methoxy-1- H benzyl 2.21579/581/583 B methyl-ethyl A35 (2,2,2- H benzyl 2.12 646/648/650 BTrifluoro- ethyl- carbamoyl)- methyl A36 3,3,3- H benzyl 2.26603/605/607 B Trifluoro- propyl A37 sec-Butyl H benzyl 2.31 563/565/567B A38 (Tetrahydro- H benzyl 2.2 591/593/595 B furan-2-yl)- methyl A39Benzyl H benzyl 2.31 597/599/601 B A40 2-Fluoro- H benzyl 2.32615/617/619 B benzyl A41 1-Phenyl-ethyl H benzyl 2.35 611/613/615 B A424-Methoxy- H benzyl 2.29 627/629/631 B benzyl A43 1,1-Dioxo- H benzyl2.07 611/613/615 B thietan-3-yl A44 (6-Chloro- H benzyl 2.24 632/634/636B pyridin-3-yl)- methyl A45 3-Fluoro- H benzyl 2.39 601/603/605 B phenylA46 Pyridin-2-yl- H benzyl 2.07 598/600/602 B methyl A47 2,5-Dimethyl- Hbenzyl 2.16 601/603/605 B 2H-pyrazol-3- yl A48 4-Methyl- H benzyl 2.34604/606/608 B thiazol-2-yl A49 3-Methyl- H benzyl 2.33 593/595/597 Bthietan-3-yl A50 1,1-Dimethyl- H benzyl 2.41 609/611/613 B 2-methyl-sulfanyl- ethyl A51 1-Oxo-thietan- H benzyl 1.99 595/597/599 B 3-yl A52Thietan-3-yl H benzyl 2.24 579/581/583 B A53 Bicyclo[2.2.1] H benzyl2.43 601/603/605 B hept-2-yl A54 Cyclobutyl H benzyl 2.28 561/563/565 BA55 2-Methane- H benzyl 1.94 597/599/601 B sulfinyl- ethyl A56 2-Methyl-H benzyl 2.23 581/583/585 B sulfanyl- ethyl A57 Tetrahydro- H benzyl2.26 594/596/598 B thiophen-3-yl

TABLE B (Ic)

Comp No. R⁶ R¹⁷ R¹⁸ R¹⁹ R²⁰ RT (min) MH⁺ Method B1 Methyl H H PropionylH 2.02 473/475/477 B B2 Methyl H H 2-Ethyl-butyryl H 2.23 515/517/519 BB3 Methyl H H 2-(1H-Tetrazol- H 1.84 527/529/531 B 5-yl)-acetyl B4Methyl H H Cyclohex-3- H 2.21 525/527/529 B enecarbonyl B5 Methyl H H2-Bromo- H 2.21 565/567/569 B butyryl B6 Methyl H H 2-Methyl- H 2.36541/543/545 B cyclohexanecarbonyl B7 Methyl H H 3-Phenyl- H 2.21549/551/553 B propionyl B8 Methyl H H 2-(1H- H 2.05 607/609/611 BBenzoimidazol- 2-ylsulfanyl)- acetyl B9 Methyl H H Tetrahydro- H 2.08515/517/519 B furan-2-carbonyl B10 Methyl H H (E)-3-Furan-2- H 2.15537/539/541 B yl-acryl B11 Methyl H H 2-Benzyloxy- H 2.24 565/567/569 Bacetyl B12 Methyl H H 2-Thiophen-2- H 2.15 541/543/545 B yl-acetyl B13Methyl H H 2-Phenoxy- H 2.22 551/553/555 B acetyl B14 Methyl H H2-Phenyl-acetyl H 2.17 535/537/539 B B15 Methyl H H 2-{3-Methyl-2- H1.95 601/603/605 B methylimino-4- oxo-thiazolidin- 5-yl}-acetyl B16Methyl H H (E)-3-(2-Chloro- H 2.3 581/583/585 B phenyl)-acryl B17 MethylH H (E)-3-(2-Fluoro- H 2.24 565/567/569 B phenyl)-acryl B18 Methyl H H4-Oxo-4-phenyl- H 2.16 577/579/581 B butyryl B19 Methyl H H(E)-4-Oxo-4-p- H 2.27 589/591/593 B tolyl-but-2- enoyl B20 Methyl H H2-(4-Chloro- H 2.29 585/587/589 B phenoxy)-acetyl B21 Methyl H H2-(2-Phenyl- H 2.3 618/620/622 B thiazol-4-yl)- acetyl B22 Methyl H H3-(1,3-Dioxo- H 2.09 618/620/622 B 1,3-dihydro- isoindol-2-yl)-propionyl B23 Methyl H H 3-Methyl-1H- H 2.35 573/575/577 B indene-2-carbonyl B24 Methyl H H 2,3-Difluoro- H 2.23 557/559/561 B benzoyl B25Methyl H H 3-Fluoro-4- H 2.02 555/557/559 B hydroxy- benzoyl B26 MethylH H Benzo[1,2,5]thiadiazole- H 2.22 579/581/583 B 5-carbonyl B27 MethylH H 4- H 2.25 567/569/571 B Methylsulfanyl- benzoyl B28 Methyl H H2,5-Dichloro- H 2.3 589/591/593 B benzoyl B29 Methyl H H 4-Methoxy- H2.16 551/553/555 B benzoyl B30 Methyl H H 4-Pyrrol-1-yl- H 2.28586/588/590 B benzoyl B31 Methyl H H 3,4-Dihydro- H 2.19 593/595/597 B2H- benzo[b][1,4]dioxepine-7- carbonyl B32 Methyl H H Biphenyl-4- H 2.38597/599/601 B carbonyl B33 Methyl H H 2-Fluoro-3- H 2.32 607/609/611 Btrifluoromethyl- benzoyl B34 Methyl H H 9H-Fluorene-4- H 2.35609/611/613 B carbonyl B35 Methyl H H Benzo[b]thiophene-5- H 2.27577/579/581 B carbonyl B36 Methyl H H 3-Methyl- H 2.29 536/538/540 Bpyridine-2- carbonyl B37 Methyl H H Cinnoline-4- H 2.07 573/575/577 Bcarbonyl B38 Methyl H H 4-Methoxy- H 2.22 557/559/561 B thiophene-3-carbonyl B39 Methyl H H Thiophene-2- H 2.15 527/529/531 B carbonyl B40Methyl H H 5-Methyl-3- H 2.26 602/604/606 B phenyl- isoxazole-4-carbonyl B41 Methyl H H 4-Oxo-4H- H 2.16 589/591/593 B chromene-2-carbonyl B42 Methyl H H 5-Pyridin-2-yl- H 2.21 604/606/608 Bthiophene-2- carbonyl B43 Methyl H H 5-Methyl-1- H 2.22 601/603/605 Bphenyl-1H- pyrazole-4- carbonyl

BIOLOGICAL EXAMPLES Spodoptera littoralis (Systemic) (Egyptian CottonLeaf Worm)

Test compounds were applied by pipette into 24 well plates and mixedwith agar. Salad seeds were placed on the agar and the multi well plateis closed by another plate which contains also agar. After 7 days theroots have absorbed the compound and the salad has grown into the lidplate. The salad leafs were now cut off into the lid plate. Spodopteraeggs were pipette through a plastic stencil on a humid gel blottingpaper and the plate closed with it. The samples are checked formortality, repellent effect, feeding behavior, and growth regulation 5days after infestation. Application rate: 12.5 ppm

The following compound gave at least 80% control of Spodopteralittoralis: A5, A17, A21, A38, A53.

Spodoptera Littoralis (Egyptian Cotton Leafworm)

Cotton leaf discs were placed on agar in a 24-well microtiter plate andsprayed with test solutions at an application rate of 200 ppm. Afterdrying, the leaf discs were infested with 5 L1 larvae. The samples werechecked for mortality, feeding behavior, and growth regulation 3 daysafter treatment (DAT).

The following compound gave at least 80% control of Spodopteralittoralis: A4, A6, A7, A9, A10, A11, A12, A13, A14, A15, A16, A17, A19,A20, A21, A22, A24, A26, A31, A32, A35, A36, A42, A43, A46, A51, A52,A54, A55, A56, A57, B1, B5, B24, B36, C1.

Heliothis Virescens (Tobacco Budworm)

Eggs (0-24 h old) were placed in 24-well microtiter plate on artificialdiet and treated with test solutions at an application rate of 200 ppm(concentration in well 18 ppm) by pipetting. After an incubation periodof 4 days, samples were checked for egg mortality, larval mortality, andgrowth regulation.

The following compound gave at least 80% control of Heliothis virescens:A12, A13, A14, A16, A17, A18, A21, A22, A26, A27, A28, A31, A35, A39,A42, A43, A44, A45, A46, A48, A51, A52, A56, A57, B1, B14, B15, B24,B27, B29, B31, B37.

Plutella Xylostella (Diamond Back Moth)

24-well microtiter plate (MTP) with artificial diet was treated withtest solutions at an application rate of 200 ppm (concentration in well18 ppm) by pipetting. After drying, the MTPs were infested with L2larvae (7-12 per well). After an incubation period of 6 days, sampleswere checked for larval mortality and growth regulation.

The following compound gave at least 80% control of Plutella xylostella:A1, A2, A3, A4, A5, A6, A7, A9, A10, A11, A12, A13, A14, A15, A16, A17,A18, A19, A21, A22, A23, A24, A25, A26, A27, A28, A31, A32, A33, A34,A35, A38, A39, A40, A42, A43, A44, A46, A47, A51, A52, A54, A55, A56,A57, B1, B24, B37, C1.

Diabrotica Balteata (Corn Root Worm)

A 24-well microtiter plate (MTP) with artificial diet was treated withtest solutions at an application rate of 200 ppm (concentration in well18 ppm) by pipetting. After drying, the MTP's were infested with L2larvae (6-10 per well). After an incubation period of 5 days, sampleswere checked for larval mortality and growth regulation.

The following compound gave at least 80% control of Diabrotica balteata:A2, A3, A10, A12, A13, A14, A18, A21, A22, A23, A26, A28, A32, A35, A43,A51, A52, A57, C1.

Myzus Persicae (Green Peach Aphid)

(Mixed Population, Feeding/Residual Contact Activity, Preventive)

Sunflower leaf discs are placed on agar in a 24-well microtiter plateand sprayed with test solutions at an application rate of 200 ppm. Afterdrying, the leaf discs are infested with an aphid population of mixedages. After an incubation period of 6 days, samples are checked formortality and special effects (e.g. phytotoxicity).

The following compounds gave at least 80% control of Myzus persicae:A18, C1.

Myzus persicae (Sachet) (Green Peach Aphid) Mixed Population

Test compounds were applied by pipette into 24 well plates and mixedwith Sucrose solution. The plates were closed with a stretched Parafilm.A plastic stencil with 24 holes is placed onto the plate and infestedpea seedlings were placed directly on the Parafilm. The infested plateis closed with a gel blotting paper and another plastic stencil and thenturned upside down. 5 days after infestation the samples were checked onmortality. Application rate: 12.5 ppm. The following compounds gave atleast 80% control of Myzus persicae: A5, A13, A16, A21, A22, A28, A52,B21.

Thrips Tabaci (Onion Thrips)

Sunflower leaf discs were placed on agar in a 24-well microtiter plateand sprayed with test solutions at an application rate of 200 ppm. Afterdrying, the leaf discs were infested with an aphid population of mixedages. After an incubation period of 7 days, samples were checked formortality.

The following compounds gave at least 80% control of Thrips tabaci: A1,A2, A4, A6, A7, A8, A9, A10, A11, A13, A14, A15, A16, A19, A20, A21,A22, A23, A24, A26, A27, A28, A35, A39, A43, A46, A52, A54, A55, A57,B1, C1.

Tetranychus Urticae (Two-Spotted Spider Mite)

Bean leaf discs on agar in 24-well microtiter plates were sprayed withtest solutions at an application rate of 200 ppm. After drying, the leafdiscs are infested with mite populations of mixed ages. 8 days later,discs are checked for egg mortality, larval mortality, and adultmortality.

The following compound gave at least 80% control of Tetranychus urticae:A2, A4, A9, A10, A13, A14, A16, A19, A20, A21, A22, A26, A27, A28, A34,A35, A42, A43, A51, A54, A55, B12, B29, B38, C1.

The invention claimed is:
 1. A compound of of formula Int-I

wherein A¹, A², A³ and A⁴ are independently of each other C—H, C—R⁷, ornitrogen; G¹ is oxygen or sulfur; R is hydroxy, C₁-C₁₆ alkoxy, orhalogen, R³ is C₁-C₈haloalkyl; R⁴ is aryl or aryl substituted by one tofive R¹¹, heteroaryl or heteroaryl substituted by one to five R¹¹; R⁵ ishydrogen; R⁶ is hydrogen, C₁-C₈alkyl or C₁-C₈alkyl substituted by one tofive R¹², C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one tofive R¹³, aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the arylmoiety is substituted by one to five R¹⁴, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R¹⁴, aryl or aryl substituted by one to fiveR¹⁴, heterocyclyl or heterocyclyl substituted by one to five R¹⁴,C₁-C₄alkoxycarbonyl-, C₁-C₄alkenyloxycarbonyl-,C₁-C₄alkynyloxycarbonyl-, or benzyloxycarbonyl- or benzyloxycarbonyl- inwhich the benzyl group is optionally substituted by one to five R¹⁶;each R⁷ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkenyl, C₁-C₈haloalkenyl, C₁-C₈alkynyl,C₁-C₈haloalkynyl, C₃-C₁₀cycloalkyl, C₁-C₈alkoxy-, C₁-C₈haloalkoxy-,C₁-C₅alkylthio-, C₁-C₈haloalkylthio-, C₁-C₅alkylsulfinyl-,C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, orC₁-C₈haloalkylsulfonyl-; each R¹¹ and R¹⁴ is independently halogen,cyano, nitro, C₁-C₈alkyl, C₁-C₈haloalkyl, C₂-C₈alkenyl,C₂-C₈haloalkenyl, C₂-C₈alkynyl, C₂-C₈haloalkynyl, hydroxy, C₁-C₈alkoxy-,C₁-C₈haloalkoxy-, mercapto, C₁-C₈alkylthio-, C₁-C₈haloalkylthio-,C₁-C₈alkylsulfinyl-, C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-,C₁-C₈haloalkylsulfonyl-, C₁-C₈alkylcarbonyl-, C₁-C₈alkoxycarbonyl-, arylor aryl substituted by one to five R¹⁵, or heterocyclyl or heterocyclylsubstituted by one to five R¹⁵; each R¹² is independently halogen,cyano, nitro, hydroxy, C₁-C₈alkoxy-, C₁-C₈haloalkoxy-,C₁-C₈alkylcarbonyl-, C₁-C₈alkoxycarbonyl-, mercapto, C₁-C₈alkylthio-,C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-, C₁-C₈haloalkylsulfinyl-,C₁-C₈alkylsulfonyl-, or C₁-C₈haloalkylsulfonyl-; each R¹³ isindependently halogen or C₁-C₈alkyl; each R¹⁵ is independently halogen,cyano, nitro, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy-, orC₁-C₄haloalkoxy-; and each R¹⁶ is independently halogen, cyano, formyl,C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy,C₃-C₆cycloalkyl; or a salt or N-oxide thereof.